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HIPEC - nowości w piśmiennictwie

Ann Surg Oncol. 2019 Sep 9. doi: 10.1245/s10434-019-07797-8. [Epub ahead of print]

Diaphragmatic Peritoneal Stripping Versus Full-Thickness Resection in CRS/HIPEC: Is There a Difference?

Authors:

Sullivan BJ1, Bekhor EY2, Carpiniello M2, Leigh NL2, Pletcher ER2, Solomon D2, Magge DR2, Sarpel U2, Labow DM2, Golas BJ2.


Abstract

Background:

Pleural recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare and poorly delineated. Specifically, data are limited on the effect that diaphragmatic peritoneal stripping versus full-thickness resection has on the nature of ipsilateral pleural recurrence and postoperative morbidity.

Methods:

Patients with peritoneal carcinomatosis who underwent CRS/HIPEC were included from a prospectively maintained database. The patients were divided into three cohorts based on surgical management of the diaphragm as follows: diaphragm-stripping (DS) cohort, full-thickness resection (FTR) cohort, and no diaphragm manipulation (ND) cohort. Postoperative morbidity and incidence of ipsilateral pleural recurrence were evaluated. All diaphragmatic defects were closed before abdominal chemoperfusion.

Discussion:

The inclusion criteria were met by 409 CRS/HIPEC procedures: 66 in DS, 122 in FTR, and 238 in ND. Ipsilateral pleural recurrence rates did not differ significantly between the three cohorts (DS 6%, FTR 3%, ND 3%; p = 0.470). Postoperative respiratory complications and overall morbidity were significantly greater for the patients who underwent diaphragmatic disruption (stripping and/or resection) than for the patients who did not (p ≤ 0.0001), but the two groups did not differ in terms of 30-day mortality. However, comparison of FTR with DS showed no impact on major morbidity or pleural recurrence.

Conclusions:

Although patients undergoing surgical manipulation of the diaphragm during CRS/HIPEC experienced significantly greater morbidity, diaphragmatic stripping did not differ from full-thickness resection in terms of grades 3 and 4 complications or incidence of ipsilateral pleural recurrences. When deemed necessary to achieve complete cytoreduction, full-thickness diaphragmatic resection should be undertaken. In addition, the data support the observation that definitive repair of the diaphragmatic defect before abdominal chemoperfusion does not adversely influence ipsilateral pleural recurrence.

Surg Oncol. 2019 Sep 5;31:33-37. doi: 10.1016/j.suronc.2019.09.002. [Epub ahead of print]

Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for patients at High-Risk of Peritoneal Metastases

Authors:

Morris MC1, Dhar VK1, Stevenson MA2, Winer LK1, Lee TC1, Wang J3, Ahmad SA1, Patel SH1, Sussman JJ1, Abbott DE4.


Abstract

Background:

Selection of patients for hyperthermic intraperitoneal chemotherapy (HIPEC) continues to evolve. We hypothesized that adjuvant HIPEC for patients at high-risk of peritoneal progression is safe and associated with favorable outcomes.

Methods:

The institutional database of a high-volume center was queried for patients with high-risk disease undergoing HIPEC with a peritoneal carcinomatosis index (PCI) of 0. High-risk patients were defined as those with ruptured primary tumors or locally advanced (T4) disease.

Results:

37 patients underwent adjuvant HIPEC, with a median follow-up of 5.2 years. 54% had low-grade (LG) tumors while 46% had high-grade (HG) tumors. No patients underwent neoadjuvant chemotherapy, while eleven patients (32.4%) received adjuvant chemotherapy. There were no perioperative mortalities, and the overall complication rate was 43%. For the entire cohort, five year recurrence-free survival (RFS) and overall survival (OS) were 77% and 100%, respectively. Five year RFS and OS were 75% and 100% for LG patients and 81% and 100% for HG patients, respectively.

Conclusions:

Adjuvant HIPEC for patients at high-risk of peritoneal progression, with PCI 0, is safe and associated with favorable long-term survival. Additional prospective investigation is needed to identify patient populations who may benefit most from HIPEC.

Cancer Med. 2019 Sep 4. doi: 10.1002/cam4.2436. [Epub ahead of print]

Peritoneal mesothelioma in Sweden: A population-based study

Authors:

Cashin PH1, Jansson Palmer G2, Asplund D3, Graf W1, Syk I4.


Abstract

The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.

Surg Endosc. 2019 Aug 27. doi: 10.1007/s00464-019-07076-3. [Epub ahead of print]

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study

Authors:

Tavernier C1,2, Passot G1,2, Vassal O3, Allaouchiche B3,4, Decullier E5, Bakrin N1,2, Alyami M1,2, Davigo A1,2, Bonnet JM4, Louzier V4, Paquet C4, Glehen O1,2, Kepenekian V6,7.


Abstract

Background:

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters.

Methods:

Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without.

Results:

The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences.

Conclusions:

In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.

World J Surg Oncol. 2019 Aug 7;17(1):138. doi: 10.1186/s12957-019-1673-x.

P.R.O.P.S. - A novel Pre-Operative Predictive Score for unresectability in patients with colorectal peritoneal metastases being considered for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Authors:

Yong ZZ1, Tan GHC1, Shannon N1, Chia C1


Abstract

Background:

Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria-Peritoneal Surface Disease Severity Score (PSDSS), Verwaal's Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability.

Methods:

Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (p < 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity.

Results:

PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity.

Conclusions:

PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.

Langenbecks Arch Surg. 2019 Aug;404(5):527-539. doi: 10.1007/s00423-019-01805-x. Epub 2019 Aug 3.

Evaluation of cytoreductive surgery and HIPEC for peritoneal surface malignancies: analysis of 384 consecutive cases

Authors:

Narasimhan V1,2, Das A3,4, Warrier S3, Lynch C3, McCormick J3, Tie J5, Michael M5, Ramsay R3,4, Heriot A3,4.


Abstract

Background:

Peritoneal surface malignancy (PSM) was historically associated with a poor survival. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can now offer patients with PSM a favourable overall survival. Here, we report our single-institute outcomes following CRS and HIPEC for PSM and evaluate changes in our practice over time.

Methods:

This is a retrospective review from 2009 to 2018 of all patients undergoing CRS and HIPEC for PSM at a statewide peritoneal disease centre. Cases were divided into the first half and second to compare changes in practice over time.

Result:

Three hundred and eighty four CRS and HIPEC cases were performed during this time. The median age was 56 years with 59.6% female. The median peritoneal carcinomatosis index (PCI) was 11, with a reduction in PCI in the second cohort (9 v 15, p < 0.01). Complete cytoreduction rates were significantly higher in the second cohort (82.3% v 67.7%, p < 0.01). Overall, grade III/IV complications occurred in 101 cases (26.3%) with three (0.8%) perioperative mortalities. Median overall survival (OS) for the entire cohort was 85 months, with a 5-year survival of 52%. Median OS was 97 months for PMP, 34 months for colorectal peritoneal metastases and 27 months for other histologies. Completeness of cytoreduction, histology type, and PCI were factors independently associated with overall survival.

Conclusions:

CRS and HIPEC can offer highly favourable outcomes for PSM with low morbidity. Successful complete cytoreduction rates improved significantly with greater experience and better patient selection.

J Turk Ger Gynecol Assoc. 2019 Jul 31. doi: 10.4274/jtgga.galenos.2019.2018.0165. [Epub ahead of print]

Secondary debulking for ovarian carcinoma relapse: The R-R dilemma – is the prognosis different for residual or recurrent disease?

Authors:

Spiliotis JD1,2, Iavazzo C3, Kopanakis ND4, Christopoulou A5.


Abstract

Objective:

To analyse the kind of ovarian cancer relapse by separating residual from recurrent disease and correlating them with patients’ survival.

Material and Methods:

Retrospective study of 200 women with ovarian carcinoma relapse during the period 2005-2017.

Result:

The main sites of residual disease included great omentum, epiploic appendices, liver round ligament, gallbladder, cervical/vaginal stump. Median survival for women with residual disease treated with cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC)+ systemic chemotherapy was 38 months compared to the control group which reached 23,8 months. The morbidity rates were 18% versus 7% respectively while the mortality rates were 2.5% versus 1.3%. The main sites of recurrent disease included mesenterium, pelvic floor, diaphragm, and Glisson’s capsule. Women with recurrent disease treated with CRS +HIPEC+ systemic chemotherapy had median survival rates of 26 months versus 16 months in the control group. The morbidity rates were 22% versus 15% respectively while the mortality rates were 3.3% versus 0%.

Conclusions:

Patients undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse have a different prognosis when comparing cases with residual to those with recurrent disease. A different prognosis is presented in women undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse when comparing cases with residual to those with recurrent disease.

Lancet Gastroenterol Hepatol. 2019 Oct;4(10):761-770. doi: 10.1016/S2468-1253(19)30239-0. Epub 2019 Jul 29.

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial

Authors:

Klaver CEL1, Wisselink DD1, Punt CJA2, Snaebjornsson P3, Crezee J4, Aalbers AGJ5, Brandt A6, Bremers AJA7, Burger JWA8, Fabry HFJ9, Ferenschild F10, Festen S11, van Grevenstein WMU12, Hemmer PHJ13, de Hingh IHJT7, Kok NFM5, Musters GD1, Schoonderwoerd L14, Tuynman JB15, van de Ven AWH16, van Westreenen HL17, Wiezer MJ18, Zimmerman DDE19, van Zweeden AA20, Dijkgraaf MGW21, Tanis PJ22; COLOPEC collaborators group.


Abstract

Background:

Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer.

Methods:

This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0-2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m2) for 30 min at 42°C, delivered simultaneously or within 5-8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086.

Findings:

Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80•9% [95% CI 73•3-88•5] for the experimental group vs 76•2% [68•0-84•4] for the control group, log-rank one-sided p=0•28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis.

Interpretation:

In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial.

Funding:

Organization for Health Research and Development and the Dutch Cancer Society.

Crit Rev Oncol Hematol. 2019 Jul 9;142:119-129. doi: 10.1016/j.critrevonc.2019.06.014. [Epub ahead of print]

Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer

Authors:

Wisselink DD1, Braakhuis LLF2, Gallo G3, van Grevenstein WMU4, van Dieren S5, Kok NFM6, de Reuver PR7, Tanis PJ8, de Hingh IHJT9.


Abstract

Background:

The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal metastases of colorectal cancer. Whether this applies to all published CRS/HIPEC regimens is unclear.

Methods:

A systematic literature search identified 46 studies on CRS/HIPEC using either oxaliplatin of mitomycin C with at least one oncological outcome parameter RESULTS: Oxaliplatin and mitomycin C studies were comparable regarding extent of disease, but differed substantially regarding synchronous versus metachronous presentation, application of neo-adjuvant systemic chemotherapy, duration of HIPEC, and completeness of cytoreduction for at least one of the oncological endpoints. Severe postoperative complication rate seemed significantly higher after oxaliplatin-based CRS/HIPEC.

Conclusions:

Published cohorts on oxaliplatin-based CRS/HIPEC differed essentially from MMC-based procedures, especially considering the application of oxaliplatin-containing neo-adjuvant systemic therapy and shorter exposure time to intraperitoneal chemotherapy in oxaliplatin studies. No meaningful comparison could be made regarding DFS and OS.

Oncol Lett. 2019 Aug;18(2):2025-2033. doi: 10.3892/ol.2019.10493. Epub 2019 Jun 19.

Ascites do not affect the rate of complete cytoreductive surgery and prognosis in patients with primary ovarian cancer with ascites treated with hyperthermic intraperitoneal chemotherapy.

Authors:

Ba M1, Long H2, Zhang X1, Yan Z1, Wang S1, Wu Y1, Gong Y1, Cui S3.


Abstract

Cytoreductive surgery (CRS) is the current standard therapy procedure for patients with advanced ovarian cancer (OC), but numerous patients with OC are complicated with ascites. The aim of the present study was to assess whether massive ascites affect the rate of complete CRS and prognosis for patients with primary OC treated with hyperthermic intraperitoneal chemotherapy (HIPEC). Between December 2006 and December 2015, 1,293 patients with primary OC from the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University prospective database were treated with CRS combined with HIPEC. A total of 1,225 patients were without malignant ascites or small amounts of ascites and 68 had massive malignant ascites. The rate of complete CRS, overall survival (OS), disease-free survival (DFS) and resolution of ascites for patients with massive ascites were analyzed between patients without/small ascites, and with massive ascites. Complete CRS was successful in 86.8% (1,063/1,225) of patients without/small ascites, and 85.3% (58/68) of patients with massive ascites. No statistical differences were identified in complete CRS success between patients with ascites and patients without/small ascites (P=0.080). For patients with massive ascites, all symptoms exhibited regression; the total objective remission rate was 100% (68/68), even for patients with incomplete CRS (10/68) (P=0.100). The mean OS was 58 months and the mean DFS was 26 months in patients without/small ascite, vs. 57 months and 28 months in patients with massive ascites. No significant differences were noted in median DFS and median OS between patients with ascites, and patients without/small ascites (All P>0.05). In conclusion, the results of the present study suggest that ascites does not affect the rate of complete CRS and the prognosis of patients with massive ascites following HIPEC. CRS is suitable for the majority of patients with primary OC and massive ascites.

Ann Surg Oncol. 2019 May 20. doi: 10.1245/s10434-019-07378-9. [Epub ahead of print]

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

Authors:

Arjona-Sanchez A1,2, Rodriguez-Ortiz L3, Baratti D4, Schneider MA5, Gutiérrez-Calvo A6, García-Fadrique A7, Tuynman JB8, Cascales-Campos PA9, Martín VC10, Morales R11, Salti GI12, Arteaga X13, Pacheco D14, Alonso-Gomez J15, Yalkin O16, Villarejo-Campos P17, Sanchez-Hidalgo JM3,18, Casado-Adam A3,18, Cosano-Alvarez A3, Rufian-Peña S3,18, Briceño J3,18.


Abstract

Background:

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients.

Methods:

We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units.

Results:

A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation.

Conclusions:

By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

https://www.ncbi.nlm.nih.gov/pubmed/31111351

Acad Radiol. 2019 May 14. pii: S1076-6332(19)30190-4. doi: 10.1016/j.acra.2019.04.005. [Epub ahead of print]

The accuracy of multi-detector computed tomography and laparoscopy in the prediction of peritoneal carcinomatosis index score in primary ovarian cancer.

Authors:

Ahmed SA1, Abou-Taleb H2, Yehia A2, El Malek NAA3, Siefeldein GS4, Badary DM5, Jabir MA6.


Abstract

Rationale and objectives:

The purpose of this study was to compare the accuracy of MDCT and laparoscopy in the prediction of peritoneal carcinomatosis index score. Reproducibility of MDCT interpretation was also assessed.

Methods:

This prospective study included 85 ovarian cancer patients underwent MDCT and diagnostic laparoscopy before cytoreductive surgery. We calculated the accuracy of diagnostic modalities in the calculation of the peritoneal cancer index score (PCI). Radiologist interobserver agreement was calculated using kappa statistics.

Results:

Nine hundred-thirty (84.2%) of the 1105 regions had peritoneal deposits at exploratory laparotomy. Computed tomography (CT) and laparoscopy sensitivity were 94.9%, 98.3%, specificity 86.7%, 80.4%, PPV 97.9 %, 96.8%, NPV 72.2%, 88.8 %, and accuracy 93.8 %, 95.7%, respectively. However, computed tomography (CT) diagnostic performance is less accurate than laparoscopy in pelvic and small intestinal regions; no statistically significant differences were evident regarding total PCI score compared to surgery (p> 0.05). CT and laparoscopy correctly depicted peritoneal carcinomatosis in 88.2%, 90.6% of patients, respectively. Optimal cytoreduction was achieved in 68 (80%) patients.

Conclusions:

Both CT and laparoscopy seems to be effective tools for assessment of peritoneal carcinomatosis using the PCI score. Dedicated MDCT protocol with routine use of a standardized PCI form may provide better comprehensive multi-regional analysis that may help surgeons referring patients to the best treatment option. Laparoscopy is a valuable tool in cases with a high risk of suboptimal cytoreduction related to disease extent.

https://www.ncbi.nlm.nih.gov/pubmed/31101436

J Clin Oncol. 2019 May 14:JCO1801688. doi: 10.1200/JCO.18.01688. [Epub ahead of print]

Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis.

Authors:

Bonnot PE1,2, Piessen G3, Kepenekian V1,2, Decullier E4, Pocard M5, Meunier B6, Bereder JM7, Abboud K8, Marchal F9, Quenet F10, Goere D11, Msika S12, Arvieux C13, Pirro N14, Wernert R15, Rat P16, Gagnière J17, Lefevre JH18, Courvoisier T19, Kianmanesh R20, Vaudoyer D1,2, Rivoire M21, Meeus P21, Passot G1,2, Glehen O1,2; FREGAT and BIG-RENAPE Networks.


Abstract

Purpose:

Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC.

Patients and methods:

From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors.

Results:

After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% (P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496).

Conclusions:

Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.

https://www.ncbi.nlm.nih.gov/pubmed/31084544

Cancer Med. 2019 Apr 29. doi: 10.1002/cam4.2204. [Epub ahead of print]

Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central-Eastern European study.

Authors:

Yarema R1, Mielko J2, Fetsych T1, Ohorchak M3, Skorzewska M2, Rawicz-Pruszyński K2, Mashukov A4, Maksimovsky V4, Jastrzębski T5, Polkowski W2, Gyrya P3, Kovalchuk Y3, Safiyan V3, Karelin I3, Kopetskiy V6, Kolesnik O6, Kondratskiy Y6, Paskonis M7.


Abstract

Background and objectives:

Clinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central-Eastern European population.

Methods:

A retrospective cooperative study was performed at 6 Central-Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10).

Results:

Postoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long-term survivors occurred in the group with peritoneal cancer index (PCI) of 0-6 points without survival difference in groups with PCI 7-12 vs PCI 13 or more points.

Conclusions:

GC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long-term survival may be expected after palliative approach to HIPEC.

https://www.ncbi.nlm.nih.gov/pubmed/31033239

BMC Cancer. 2019 Apr 25;19(1):390. doi: 10.1186/s12885-019-5545-0.

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parralel-group, phase II-III, randomised, superiority study (CAIRO6).

Authors:

Rovers KP1, Bakkers C1, Simkens GAAM1, Burger JWA1, Nienhuijs SW1, Creemers GM2, Thijs AMJ2, Brandt-Kerkhof ARM3, Madsen EVE3, Ayez N3, de Boer NL3, van Meerten E4, Tuynman JB5, Kusters M5, Sluiter NR5, Verheul HMW6, van der Vliet HJ6, Wiezer MJ7, Boerma D7, Wassenaar ECE7, Los M8, Hunting CB8, Aalbers AGJ9, Kok NFM9, Kuhlmann KFD9, Boot H10, Chalabi M10, Kruijff S11, Been LB11, van Ginkel RJ11, de Groot DJA12, Fehrmann RSN12, de Wilt JHW13, Bremers AJA13, de Reuver PR13, Radema SA14, Herbschleb KH14, van Grevenstein WMU15, Witkamp AJ15, Koopman M16, Haj Mohammad N16, van Duyn EB17, Mastboom WJB17, Mekenkamp LJM18, Nederend J19, Lahaye MJ20, Snaebjornsson P21, Verhoef C3, van Laarhoven HWM22, Zwinderman AH23, Bouma JM24, Kranenburg O25, van 't Erve I21, Fijneman RJA21, Dijkgraaf MGW23, Hemmer PHJ11, Punt CJA22, Tanis PJ26, de Hingh IHJT27; Dutch PeritonealOncology Group (DPOG); Dutch Colorectal Cancer Group (DCCG).


Abstract

Background:

Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes.

Methods:

This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates.

Discussion:

This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapyand CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM.

Trial registration:

Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99

https://www.ncbi.nlm.nih.gov/pubmed/31023318

Langenbecks Arch Surg. 2019 Apr 25. doi: 10.1007/s00423-019-01787-w. [Epub ahead of print]

Synchronous liver metastases and peritoneal carcinomatosis from colorectal cancer: different strategies for curative treatment?

Authors:

Pinto A1,2, Hobeika C2, Philis A1, Kirzin S1, Carrère N1, Ghouti L3.


Abstract

Background:

Management of patients with resectable hepatic metastases (HMs) and colorectal peritoneal carcinomatosis (CRPC) is not currently standardised.

Objective:

The aims of this study were to evaluate the safety of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and hepatic surgery for patients with CRPC with synchronous hepatic metastases (HM), and its impact on survival rates.

Methods:

A retrospective analysis was performed, including patients undergoing CRS/HIPEC for CRPC from 2007 to September 2016 in two groups, with (HM+) and without (HM-) synchronous hepatic metastases. Patients with extra-abdominal metastases were excluded. The hepatic strategy was described. Morbimortality and survival were compared between the two groups.

Result:

One hundred nine patients underwent CRS/HIPEC for CRPC with or without hepatic surgery with curative intent: 33 patients with (HM+) and 76 patients without (HM-) synchronous HM. The median follow-up was 30 months. All patients with HM (HM+) received neoadjuvant chemotherapy vs. 88.1% in the HM- group (p = 0.04) associated with monoclonal antibody in 66.6% of cases in the HM+ group vs. 57% in the HM- group (p = 0.01). In the HM+ group, two steps were implemented to treat peritoneal and hepatic metastases in 15 patients (45%). In this group, planned hepatic resection in two procedures was performed for eight patients, all presenting bilobar HM. Postoperative morbidity did not differ between the two groups. No deaths occurred. Median overall survival (OS) and recurrence-free survival (RFS) were 31 and 65 months (p = 0.188), versus 21 and 24 months (p = 0.119), respectively, in the HM+ versus HM- groups. In multivariate analysis, the peritoneal cancer index (PCI) was the only significant prognostic factor whereas synchronous HM was not a significant prognostic factor.

Conclusions:

Curative surgical treatment for CRPC with synchronous HM seems to be feasible and safe, and could facilitate long survival rates, compared to patients without HM. The hepatic strategy is not standardised. However, a "two-step" surgical strategy could be proposed in order to reduce postoperative morbidity rates.

https://www.ncbi.nlm.nih.gov/pubmed/31025165

Eur J Surg Oncol. 2019 Apr 1. pii: S0748-7983(19)30379-8. doi: 10.1016/j.ejso.2019.03.034. [Epub ahead of print]

Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases of urachal cancer.

Authors:

Mertens LS1, Behrendt MA2, Mehta AM3, Stokkel L4, de Jong J5, Boot H6, Horenblas S4, van der Heijden MS7, Moonen LM8, Aalbers AGJ9, Meinhardt W4, van Rhijn BWG10.


Abstract

Introduction:

Urachal adenocarcinoma (UrAC) is a rare malignancy arising from persistent urachal remnants, which can cause peritoneal metastases (PM). Currently, patients with this stage UrAC are considered beyond cure. Our objective is to report long-term oncological outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PM of urachal adenocarcinoma (UrAC).

Materials and methods:

We identified 55 patients with UrAC treated at our hospital between 1994 and 2017. Patients were staged with CT, bone scintigraphy and/or PET/CT. From 2001 on, cN0M0 patients underwent staging laparoscopy. Ten patients had PM and were treated with CRS/HIPEC; 35 showed no metastases and underwent local treatment; 10 had distant metastases and received palliative chemotherapy. Disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and log-rank tests. Postoperative complications represent a secondary outcome.

Results:

The median follow-up was 96.8 months. Of the CRS/HIPEC patients, 5 (50%) developed a recurrence; 4 (40%) died of disease. The 2-yr and 5-yr DSS after CRS/HIPEC were 66.7% and 55.6%, respectively. DSS of the CRS/HIPEC patients did not significantly differ from DSS of patients without metastases who only underwent curative local treatment and was superior to patients with distant metastases (P = 0.012). The overall complication rate after CRS/HIPEC was 60%. Major complications (Clavien 3) constituted 20%. The study is limited by its retrospective nature and the small sample size.

Conclusion:

CRS/HIPEC demonstrates satisfactory long-term oncological outcome for patients with PM of UrAC. It may be offered as a potentially curative treatment option for this group of patients.

https://www.ncbi.nlm.nih.gov/pubmed/31003721

Arch Gynecol Obstet. 2019 May 1. doi: 10.1007/s00404-019-05167-z. [Epub ahead of print]

Treatments and overall survival in patients with Krukenberg tumor

Authors:

Lionetti R1, De Luca M1, Travaglino A2, Raffone A3, Insabato L4, Saccone G3, Mascolo M4, D'armiento M5, Zullo F3, Corcione F1.


Abstract

Background:

Krukenberg tumor (KT) is a rare secondary ovarian tumor, primarily localized at the gastrointestinal tract in most cases. KT is related to severe prognosis due to its aggressiveness, diagnostic difficulties and poor treatment efficacy. Several treatments have been used, such as cytoreductive surgery (CRS), adjuvant chemotherapy (CT) and/or hyperthermic intraperitoneal chemotherapy (HIPEC). To date, it is still unclear which treatment or combination of treatments is related to better survival.

Objective:

To assess the most effective therapeutic protocol in terms of overall survival (OS).

Methods:

A systematic review of the literature was performed by searching MEDLINE, Scopus, EMBASE, ClinicalTrial.gov, OVID, Web of Sciences, Cochrane Library, and Google Scholar for all studies assessing the association of treatments with OS in KTs. The effectiveness of each treatment protocol was evaluated by comparing the OS between patients treated with different treatment protocols.

Results:

Twenty retrospective studies, with a total sample size of 1533 KTs, were included in the systematic review. Therapeutic protocols used were CRS in 18 studies, CT in 13 studies, HIPEC in 7 studies, neoadjuvant CT in 2 studies, and some combinations of these in 6 studies. Seven studies showed that CRS significantly improved OS compared to other treatments or association of treatments without it. 11 studies showed that CRS without residual (R0 CRS) had a significantly better OS than CRS with residual (R + CRS). Five studies showed that CT significantly improved OS, but other five showed it did not. Two studies showed that HIPEC in association with CRS improved OS, while another study showed that efficacy of HIPEC was comparable to CT. Two studies evaluated neoadjuvant CT, but results were conflicting.

Conclusions:

CRS and in particular R0 CRS are the treatments showing the clearest results in improving OS in KT patients. Results about CT are conflicting. HIPEC appears effective both alone and in combination with CRS, and also related to fewer adverse effect than CT. The usefulness of neoadjuvant CT is still unclear. The association of R0 CRS with HIPEC seems to be the most effective and safe therapeutic protocol for KT patients.

https://www.ncbi.nlm.nih.gov/pubmed/31044302

J Ovarian Res. 2019 Apr 17;12(1):33. doi: 10.1186/s13048-019-0509-1.

The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis

Authors:

Zhang G1, Zhu Y2, Liu C1, Chao G1, Cui R1, Zhang Z3.


Abstract

Background and objective:

Previous studies about the prognostic value of the HIPEC have yielded controversial results. Therefore, this study aims to assess the impact of HIPEC on patients with ovarian cancer.

Results:

We included 13 comparative studies, and found that the overall survival (OS) and progression-free survival (PFS) in HIPECgroups were superior to groups without HIPEC treatment in the all total population (HR = 0.54,95% CI:0.45 to 0.66, HR = 0.45, 95% CI: 0.32 to 0.62). Additionally, the subgroup analysis showed that patients with advanced primary ovarian cancers also gained improved OS and PFS benefit from HIPEC (HR = 0.59,95% CI:0.46 to 0.75, HR = 0.41,95% CI:0.32 to 0.54). With regard to recurrent ovarian cancer, HIPEC was associated with improved OS (HR = 0.45,95% CI:0.24 to 0.83), but for the PFS, no correlation was observed between HIPC group and the non-HIPEC group (HR = 0.55,95% CI:0.27 to 1.11). HIPEC also led to favorable clinical outcome (HR = 0.64,95% CI:0.50 to 0.82, HR = 0.36,95% CI:0.20 to 0.65) for stage III or IV ovarian cancer with initial diagnosis.

Conclusions:

The review indicated that HIPEC-based regimens was correlated with better clinical prognosis for patients with primary ovarian cancers. For recurrent ovarian cancers, HIPEC only improved the OS but did not elicit significant value on the PFS.

https://www.ncbi.nlm.nih.gov/pubmed/30995948

J Gastrointest Surg. 2019 May 14. doi: 10.1007/s11605-019-04239-4. [Epub ahead of print]

Outcomes Following Cytoreduction and HIPEC for Pseudomyxoma Peritonei: 10-Year Experience

Authors:

Narasimhan V1,2, Wilson K3,4, Britto M3, Warrier S3, Lynch AC3, Michael M4,5, Tie J5, Akhurst T4, Mitchell C4, Ramsay R3,4, Heriot A3,4.


Abstract

Background:

Pseudomyxoma peritonei (PMP) is a rare clinical presentation, with considerable morbidity and mortality if left untreated. In recent decades, there is growing acceptance for the use of cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC). The aim of this study was to report on our 10-year single-center experience on outcomes following CRS and HIPEC for PMP of appendiceal origin.

Methods:

A retrospective analysis of a prospectively maintained database of all patients undergoing CRS and HIPEC for PMP of appendiceal origin over a 10-year period at a statewide referral center was conducted.

Results:

One hundred and seventy-five cytoreductive procedures were undertaken in 140 patients. The mean patient age was 57.4 years, with a female preponderance (56%). The median PCI was 16, with 73.1% of cases having a complete cytoreduction. Grade III/IV complications occurred in 36 (20.6%) cases, with no mortalities. The median overall and disease-free survival was 100 months and 40 months, respectively, with a 71% 5-year survival. High-grade histology was the main factor identified as an independent predictor of worse overall survival.

Conclusions:

CRS and HIPEC are safe with acceptable rates of morbidity. It can provide very favorable survival in patients with PMP. High-grade histology is a key prognostic factor associated with a worse overall survival.

https://www.ncbi.nlm.nih.gov/pubmed/31090036

HIPEC - baza danych

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Ośrodki wykonujące zabiegi cytoredukcyjne HIPEC:

Ośrodek Leczenia Nowotworów Otrzewnej
Uniwersyteckie Centrum Kliniczne w Gdańsku

Kod ośrodka GDA01
80-214 Gdańsk
ul. Smoluchowskiego 17
prof. nadzw. dr hab. med. Tomasz Jastrzębski
tel. 58 349-32-12
58 349-31-90 (sekret.)

Klinika Chirurgii Onkologicznej
Uniwersytet Medyczny w Lublinie

Kod ośrodka LUB01
20-081 Lublin
ul. Staszica 11
prof. dr hab. med. Wojciech Polkowski
tel. 81 534-43-13
81 534-43-13 (sekret.)

Klinika Chirurgii Onkologicznej
Centrum Onkologii – Bydgoszcz

Kod ośrodka BYD01
85-796 Bydgoszcz
ul. Romanowskiej 2
prof. dr hab. med. Wojciech Zegarski
tel. 52 374-34-13
52 374-34-12

Klinika Chirurgii Onkologicznej I
Dolnąśląskie Centrum Onkologii we Wrocławiu

Kod ośrodka WRO01
53-413 Wrocław
pl. Hirszfelda 12
prof. dr hab. med. Marek Bębenek
tel. 71 36-89-301

Klinika Gastroenterologii Onkologicznej
Centrum Onkologii – Instytut

Kod ośrodka WAW01
02-781 Warszawa
ul. Roentgena 5
dr med. Tomasz Olesiński
tel. 22 546-24-92

Klinika Chirurgii Ogólnej, Onkologicznej i Gastroenterologicznej
Szpital Uniwersytecki w Krakowie

Kod ośrodka KRA01
31-501 Kraków
ul. M.Kopernika 36
prof. dr hab. med. Piotr Richter
tel. 12 424-80-42

Klinika Chirurgii Onkologicznej
Wojewódzkie Wielospecjalistyczne
Centrum Onkologii i Traumatologii
im. M.Kopernika w Łodzi

Kod ośrodka LOD01
93-509 Łódź
ul. Padereswskiego 4
prof. dr hab. med. Arkadiusz Jeziorski
tel. 42 689-54-41

Szpital Specjalistyczny Brzeziny
Kod ośrodka BRZ01
ul. Marii Curie – Skłodowskiej 6
95-060 Brzeziny
dr hab. med. Tomasz Jastrzębski
tel. 502 337 792