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Annals of Surgical Oncology (2020)

Defining “Complete Cytoreduction” After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for the Histopathologic Spectrum of Appendiceal Carcinomatosis

Authors:

Carlos A. Munoz-Zuluaga MD, Mary C. King BS, Victor S. Diaz-Sarmiento MD, Kimberley Studeman MD, Michelle Sittig RN, Ryan MacDonald PhD, Carol Nieroda MD, Katherin Zambrano-Vera MD, Vadim Gushchin MD, FACS & Armando Sardi MD, FACS

Annals of Surgical Oncology (2020)

Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative

Authors:

Adriana C. Gamboa MD, MS, Rachel M. Lee MD, MSPH, […]Charles A. Staley MD

Annals of Surgical Oncology (2020)

Clinical Implications of Genetic Signatures in Appendiceal Cancer Patients with Incomplete Cytoreduction/HIPEC

Authors:

Omeed Moaven MD, Jing Su PhD, Guangxu Jin PhD, Konstantinos I. Votanopoulos MD, PhD, Perry Shen MD, Christopher Mangieri MD, Stacey S. O’Neill MD, PhD, Kathleen C. Perry MSc, Edward A. Levine MD & Lance D. Miller PhD

Annals of Surgical Oncology volume 27, pages3516–3524(2020)

Extent of Peritoneal Metastases on Preoperative DW-MRI is Predictive of Disease-Free and Overall Survival for CRS/HIPEC Candidates with Colorectal Cancer

Authors:

Maurits P. Engbersen MSc, Arend G. J. Aalbers MD, Iris Van‘t Sant-Jansen MD, Jeroen D. R. Velsing MD, Doenja M. J. Lambregts MD, PhD, Regina G. H. Beets-Tan MD, PhD, Niels F. M. Kok MD, PhD & Max J. Lahaye MD, PhD

Annals of Surgical Oncology volume 27, pages2997–3008(2020)

Surgeons’ Ability to Predict the Extent of Surgery Prior to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

Authors:

Judith E. K. R. Hentzen MD, Willemijn Y. van der Plas BSc, Lukas B. Been MD, PhD, Frederik J. H. Hoogwater MD, PhD, Robert J. van Ginkel MD, PhD, Gooitzen M. van Dam MD, PhD, Patrick H. J. Hemmer MD & Schelto Kruijff MD, PhD

Annals of Surgical Oncology volume 27, pages3097–3102(2020)

Assessment of the Surgical Workforce Pertaining to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in the United States

Authors:

Darryl Schuitevoerder MBBS, Scott K. Sherman MD, Francisco J. Izquierdo MD, Oliver S. Eng MD & Kiran K. Turaga MD, MPH

Annals of Surgical Oncology (2020)

A Phase II Trial of Cytoreduction, Gastrectomy, and Hyperthermic Intraperitoneal Perfusion with Chemotherapy for Patients with Gastric Cancer and Carcinomatosis or Positive Cytology

Authors:

Brian Badgwell MD, MS, Naruhiko Ikoma MD, MS, Mariela Blum Murphy MD, Xuemei Wang MS, Jeannelyn Estrella MD, Sinchita Roy-Chowdhuri MD, PhD, Prajnan Das MD, Bruce D. Minsky MD, Elizabeth Lano MD, Shumei Song PhD, Paul Mansfield MD & Jaffer Ajani MD

Annals of Surgical Oncology (2020)

Repeat Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Is Not Associated with Prohibitive Complications: Results of a Multiinstitutional Retrospective Study

Authors:

Benjamin D. Powers MD, MS, Seth Felder MD, […]Sean P. Dineen MD, FACS

Annals of Surgical Oncology volume 27, pages2548–2556(2020)

Predicting Aborted Hyperthermic Intraperitoneal Chemotherapy (AHIPEC) with Preoperative Tumor and Inflammatory Markers in Potentially Resectable Appendiceal Cancer Patients with Peritoneal Carcinomatosis

Authors:

Ekaterina Baron MD, Vladimir Milovanov MD, Vadim Gushchin MD, FACS, Michelle Sittig RN, Carol Neiroda MD & Armando Sardi MD, FACS

Annals of Surgical Oncology (2020)

Pelvic Anastomosis Without Protective Ileostomy is Safe in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Authors:

Ekaterina Baron MD, Vadim Gushchin MD, FACS, Mary Caitlin King BS, Andrei Nikiforchin MD & Armando Sardi MD, FACS

Annals of Surgical Oncology (2020)

Dextrose-Containing Carrier Solution for Hyperthermic Intraperitoneal Chemotherapy: Increased Intraoperative Hyperglycemia and Postoperative Complications

Authors:

Robert J. Torphy MD, Camille Stewart MD, Piyush Sharma MD, Alison L. Halpern MD, Kristen Oase PA-C, Whitney Herter PA-C, Christan Bartsch MPH, PA-C, Chloe Friedman MPH, Marco Del Chiaro MD, PhD, Richard D. Schulick MD, MBA, Ana Gleisner MD, PhD, Martin D. McCarter MD & Steven A. Ahrendt MD

Annals of Surgical Oncology volume 27, pages2468–2475(2020)

Diagnostic Laparoscopy and Abdominal Cytology Reliably Detect Peritoneal Metastases in Patients with Urachal Adenocarcinoma

Authors:

Laura E. Stokkel MD, Akash M. Mehta MD, Mark A. Behrendt MD, Jeroen de Jong MD, PhD, Elise M. Bekers MD, Kees Hendricksen MD, PhD, Arend G. J. Aalbers MD, Niels F. M. Kok MD, PhD, Wim Meinhardt MD, PhD, Laura S. Mertens MD, PhD & Bas W. G. van Rhijn MD, PhD, FEBU

Annals of Surgical Oncology (2020)

Total Parietal Peritonectomy Can Be Performed with Acceptable Morbidity for Patients with Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: Results From a Prospective Multi-centric Study

Authors:

Aditi Bhatt MS, MCh, Praveen Kammar MS, MCh, Snita Sinukumar MS, MCh, Loma Parikh MD, Nutan Jumle MD, Sakina Shaikh BHMS, MBA & Sanket Mehta DNB

Annals of Surgical Oncology (2020)

Peritoneal Cell-Free Tumor DNA as Biomarker for Peritoneal Surface Malignancies

Authors:

Katie M. Leick MD, MS, Austin G. Kazarian BS, Maheen Rajput MD, Ann Tomanek-Chalkley BS, Ann Miller PhD, Hannah R. Shrader BA, BS, Ashley McCarthy BS, MPH, Kristen L. Coleman PhD, Pashtoon M. Kasi MD, MS & Carlos H. F. Chan MD, PhD

Annals of Surgical Oncology volume 27, pages2985–2996(2020)

The Pathologic Peritoneal Cancer Index (PCI) Strongly Differs From the Surgical PCI in Peritoneal Metastases Arising From Various Primary Tumors

Authors:

Aditi Bhatt MS, MCh, Yutaka Yonemura MD, PhD, Sanket Mehta DNB, Nazim Benzerdjeb MD, PhD, Praveen Kammar MS, MCh, Loma Parikh MD, Aruna Prabhu MS, MCh, Suniti Mishra MD, Mita Shah MD, Sakina Shaikh BHMS, Vahan Kepenekian MD, Isabelle Bonnefoy MD, Mahesh D. Patel MS, MCh, Sylvie Isaac MD, PhD & Olivier Glehen MD, PhD

Annals of Surgical Oncology volume 27, pages3259–3267(2020)

Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases

Authors:

Joel M. Baumgartner MD, MAS, Paul Riviere BS, Richard B. Lanman MD, Kaitlyn J. Kelly MD, Jula Veerapong MD, Andrew M. Lowy MD & Razelle Kurzrock MD

Annals of Surgical Oncology (2020)

Primary Tumor Location and Outcomes After Cytoreductive Surgery and Intraperitoneal Chemotherapy for Peritoneal Metastases of Colorectal Origin

Authors:

Mohammad Adileh MD, Jonathan B. Yuval MD, Henry S. Walch MS, Walid K. Chatila MS, Rona Yaeger MD, Julio Garcia-Aguilar MD, PhD, Nikolaus Schultz PhD, Philip B. Paty MD, Andrea Cercek MD & Garrett M. Nash MD, MPH

Annals of Surgical Oncology volume 27, pages2762–2773(2020)

Synchronous and Metachronous Peritoneal Metastases in Patients with Left-Sided Obstructive Colon Cancer

Authors:

Joyce Valerie Veld MD, Daniel Derk Wisselink MD, Femke Julie Amelung MD, PhD, Esther Catharina Josephina Consten MD, PhD, Johannes Hendrik Willem de Wilt MD, PhD, Ignace de Hingh MD, PhD, Wilhelmus Adrianus Bemelman MD, PhD, Jeanin Elise van Hooft MD, PhD, MBA, Pieter Job Tanis MD, PhD & Dutch Snapshot Research Group

BMC Cancer. 2020 Mar 17;20(1):224. doi: 10.1186/s12885-020-6701-2

Study protocol of a multicenter phase III randomized controlled trial investigating the efficiency of the combination of neoadjuvant chemotherapy (NAC) and neoadjuvant laparoscopic intraperitoneal hyperthermic chemotherapy (NLHIPEC) followed by R0 gastrectomy with intraoperative HIPEC for advanced gastric cancer (AGC): dragon II trial

Authors:

Beeharry MK1, Ni ZT1, Yang ZY1, Zheng YN1, Feng RH1, Liu WT2, Yan C1, Yao XX1, Li C1, Yan M1, Zhu ZG3


Abstract

Background:

Even though treatment modalities such as adjuvant systemic radio-chemotherapy and neoadjuvant chemotherapy (NAC) have individually have improved overall survival (OS) and progression-free survival (PFS) rates in advanced Gastric Cancer (AGC), the peritoneum still presides as a common site of treatment failure and disease recurrence. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) has been acknowledged as prophylaxis for peritoneal carcinomatosis (PC) in AGC patients and in this study, we aim at investigating the safety and efficacy of the combination of neoadjuvant laparoscopic HIPEC (NLHIPEC) with NAC in the neoadjuvant phase followed by surgery of curative intent with intraoperative HIPEC followed by adjuvant chemotherapy (AC).

Methods:

In this multicenter Phase III randomized controlled trial, 326 patients will be randomly separated into 2 groups into a 1:1 ratio after laparoscopic exploration. The experiment arm will receive the proposed comprehensive Dragon II regimen while the control group will undergo standard R0 D2 followed by 8 cycles of AC with oxaliplatin with S-1 (SOX) regimen. The Dragon II regimen comprises of 1 cycle of NLHIPEC for 60mins at 43 ± 0.5 °C with 80 mg/m2 of Paclitaxel followed by 3 cycles of NAC with SOX regimen and after assessment, standard R0 D2 gastrectomy with intraoperative HIPEC followed by 5 cycles of SOX regimen chemotherapy. The end-points for the study are 5 year PFS, 5 year OS, peritoneal metastasis rate (PMR) and morbidity rate.

Discussion:

This study is one of the first to combine NLHIPEC with NAC in the preoperative phase which is speculated to provide local management of occult peritoneal carcinomatosis or peritoneal free cancer cells while NAC will promote tumor downsizing and down-staging. The addition of the intraoperative HIPEC is speculated to manage dissemination due to surgical trauma. Where the roles of intraoperative HIPEC and NAC have individually been investigated, this study provides innovative insight on a more comprehensive approach to management of AGC at high risk of peritoneal recurrence. It is expected that the combination of NLHIPEC with NAC and HIPEC will increase PFS by 15% and decrease PMR after gastrectomy of curative intent.

BMC Cancer. 2019 May 6;19(1):420. doi: 10.1186/s12885-019-5640-2

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

Authors:

Koemans WJ1, van der Kaaij RT2, Boot H3, Buffart T3, Veenhof AAFA2, Hartemink KJ2, Grootscholten C3, Snaebjornsson P4, Retel VP5, van Tinteren H6, Vanhoutvin S6, van der Noort V6, Houwink A7, Hahn C7, Huitema ADR8, Lahaye M9, Los M10, van den Barselaar P11, Imhof O11, Aalbers A2, van Dam GM12, van Etten B12, Wijnhoven BPL13, Luyer MDP14, Boerma D15, van Sandick JW2


Abstract

Background:

At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy.

Methods:

In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression.

Discussion:

The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only.

Ann Surg Oncol. 2020 Mar 13. doi: 10.1245/s10434-020-08327-7. [Epub ahead of print]

Synchronous and Metachronous Peritoneal Metastases in Patients with Left-Sided Obstructive Colon Cancer

Authors:

Veld JV1,2, Wisselink DD1, Amelung FJ3,4, Consten ECJ3,5, de Wilt JHW6, de Hingh I7, Bemelman WA1, van Hooft JE2, Tanis PJ8; Dutch Snapshot Research Group


Abstract

Background:

Controversy exists on emergency setting as a risk factor for peritoneal metastases (PM) in colon cancer patients. Data in patients with obstruction are scarce. The aim of this study was to determine the incidence of synchronous and metachronous PM, risk factors for the development of metachronous PM, and prognostic implications within a large nationwide cohort of left-sided obstructive colon cancer (LSOCC).

Methods:

Patients with LSOCC treated between 2009 and 2016 were selected from the Dutch ColoRectal Audit. Additional treatment and long-term outcome data were retrospectively collected from original patient files in 75 hospitals in 2017.

Results:

In total, 3038 patients with confirmed obstruction and without perforation were included. Synchronous PM (at diagnosis or < 30 days postoperatively) were diagnosed in 148/2976 evaluable patients (5.0%), and 3-year cumulative metachronous PM rate was 9.9%. Multivariable Cox regression analyses revealed pT4 stage (HR 1.782, 95% CI 1.191-2.668) and pN2 stage (HR 2.101, 95% CI 1.208-3.653) of the primary tumor to be independent risk factors for the development of metachronous PM. Median overall survival in patients with or without synchronous PM was 20 and 63 months (p < 0.001) and 3-year overall survival of patients that did or did not develop metachronous PM was 48.1% and 77.0%, respectively (p < 0.001).

Conclusions:

This population based study revealed a 5.0% incidence of synchronous peritoneal metastases in patients who underwent resection of left-sided obstructive colon cancer. The subsequent 3-year cumulative metachronous PM rate was 9.9%, with advanced tumor and nodal stage as independent risk factors for the development of PM.

Can J Surg. 2020 Feb 21;63(1):E71-E79. doi: 10.1503/cjs.002519.

Evaluation of repeat cytoreductive surgery and heated intraperitoneal chemotherapy for patients with recurrent peritoneal carcinomatosis from appendiceal and colorectal cancers: a multicentre Canadian study

Authors:

Jost E1, Mack LA1, Sideris L1, Dube P1, Temple W1, Bouchard-Fortier A1.


Abstract

Background:

Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin.

Methods:

Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery.

Results:

Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III–IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months.

Conclusions:

Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.

Ann Surg Oncol. 2020 Feb 12. doi: 10.1245/s10434-020-08237-8. [Epub ahead of print]

Surgeons' Ability to Predict the Extent of Surgery Prior to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

Authors:

Hentzen JEKR1, van der Plas WY2, Been LB2, Hoogwater FJH3, van Ginkel RJ2, van Dam GM2,4, Hemmer PHJ2, Kruijff S2.


Abstract

Background:

The extent of surgery (ES) during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is a well-known risk factor for major postoperative morbidity. Interestingly, the reliability of surgeons to predict the ES prior to CRS + HIPEC is unknown.

Methods:

In this prospective, observational cohort study, five surgeons predicted the ES prior to surgery in all consecutive patients with peritoneal metastases (PM) who were scheduled for CRS + HIPEC between March 2018 and May 2019. After the preoperative work-up for CRS + HIPEC was completed, all surgeons independently predicted, for each individual patient, the resection or preservation of 22 different anatomical structures and the presence of a stoma post-HIPEC according to a standardized ES form. The actual ES during CRS + HIPEC was extracted from the surgical procedure report and compared with the predicted ES. Overall and individual positive (PPV) and negative predictive values (NPV) for each anatomical structure were calculated.

Results:

One hundred and thirty-one ES forms were collected from 32 patients who successfully underwent CRS + HIPEC. The number of resections was predicted correctly 24 times (18.3%), overestimated 57 times (43.5%), and underestimated 50 times (38.2%). Overall PPVs for the different anatomical structures ranged between 33.3 and 87.8%. Overall, NPVs ranged between 54.9 and 100%, and an NPV > 90% was observed for 12 anatomical structures.

Conclusions:

Experienced surgeons seem to be able to better predict the anatomical structures that remain in situ after CRS + HIPEC, rather than predict the resections that were necessary to achieve a complete cytoreduction.

Ann Surg Oncol. 2020 Feb 12. doi: 10.1245/s10434-020-08206-1. [Epub ahead of print]

Diagnostic Laparoscopy and Abdominal Cytology Reliably Detect Peritoneal Metastases in Patients with Urachal Adenocarcinoma

Authors:

Stokkel LE1, Mehta AM2,3, Behrendt MA1, de Jong J4, Bekers EM4, Hendricksen K1, Aalbers AGJ2, Kok NFM2, Meinhardt W1, Mertens LS1, van Rhijn BWG5,6.


Abstract

Background:

Urachal adenocarcinoma (UrAC) is a rare malignancy that can cause peritoneal metastases (PM). Analogous to other enteric malignancies, selected patients with limited PM of UrAC can be treated by cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objective:

The aim of this study was to address the value of diagnostic laparoscopy (DLS) and abdominal cytology (ACyt) for the detection and evaluation of the extent of PM in patients with UrAC.

Methods:

A consecutive series of cN0M0 patients with UrAC who underwent DLS with or without ACyt at a tertiary referral center between 2000 and 2018 was assessed. Patients were staged with computed tomography (CT) and/or positron emission tomography (PET)/CT or bone scan. DLS was performed to rule out PM and to evaluate the extent and resectability of PM if seen on imaging. Sensitivity and specificity values were calculated for imaging, DLS, ACyt, and the combination of DLS and ACyt.

Results:

Thirty-two patients with UrAC underwent DLS. ACyt was obtained in 19 patients. Four patients had suspicion of PM on imaging. In the 28 patients who were PM-negative on imaging, DLS and ACyt revealed PM in 6 (21%) patients, of whom 5 had macroscopically visible PM; 1 patient had positive ACyt without visible PM. Sensitivity of combined DLS/ACyt for the detection of PM was 91%, with a specificity of 100%, whereas sensitivity of imaging was 36%. DLS correctly predicted resectability in all patients.

Conclusions:

Combined DLS/ACyt proved an effective tool to detect occult PM and to evaluate the extent of PM to select UrAC patients for possible treatment with CRS/HIPEC.

Colorectal Dis. 2020 Feb 6. doi: 10.1111/codi.15003. [Epub ahead of print]

Prognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis

Authors:

Narasimhan V1,2, Tan S1, Kong J1,2, Pham T1, Michael M3, Ramsay R1,2, Warrier S1, Heriot A1,2.


Abstract

Aim:

Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM.

Methods:

A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM.

Results:

Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis.

Conclusions:

This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.

Asian J Endosc Surg. 2020 Jan 29. doi: 10.1111/ases.12784. [Epub ahead of print]

Laparoscopic hyperthermic intraperitoneal chemotherapy for appendiceal tumors

Authors:

Sommariva A1, Tonello M1, De Simoni O1, Barina A1, Riccardo Rossi C2, Pilati P1


Abstract

Introduction:

The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low-grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence.

Materials and surgical technique:

Three patients with LAMN previously treated outside our department were selected for second-look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10-mm trocars were inserted-one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m2 and cisplatin 90 mg/m2 for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow-up of 36 months, all patients were asymptomatic with no evidence of recurrence.

Discussion:

Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach.

Surg Endosc. 2020 Jan 28. doi: 10.1007/s00464-019-07349-x. [Epub ahead of print]

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms

Authors:

Abudeeb H1, Selvasekar CR1, O'Dwyer ST1,2, Chakrabarty B1, Malcolmson L1, Renehan AG1,2, Wilson MS1,2, Aziz O3,4


Abstract

Introduction:

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei (PMP) from perforated low-grade appendiceal mucinous neoplasms (LAMN II). In a selected group of LAMN II patients without established PMP, CRS/HIPEC can be performed laparoscopically (L-CRS/HIPEC); however the short-term benefits and safety of this approach have yet to be determined. This study aims to determine the short-term outcomes from a series of L-CRS/HIPEC LAMN II patients compared to those who have undergone a similar open operation (O-CRS/HIPEC) for low-volume PMP.

Methods:

LAMN II patients undergoing L-CRS/HIPEC at a UK national peritoneal tumour centre were compared to O-CRS/HIPEC patients (peritoneal cancer index ≤ 7). Outcomes of interest included Clavien-Dindo complication grade, operative time, blood transfusions, high dependency unit (HDU) admission, length of hospital stay, and histopathological findings.

Results:

55 L-CRS/HIPEC were compared to 29 O-CRS/HIPEC patients (2003-2017). Groups were matched for age, sex, and procedures. Median operative time was 8.8 (IQR 8.1-9.5) h for L-CRS/HIPEC versus 7.3 (IQR 6.7-8) h for O-CRS/HIPEC (Mann-Whitney test p < 0.001). Post-operative HDU admission was 56% versus 97% (OR 0.04 95% CI 0.01-0.34) and median length of stay = 6 (IQR 5-8) versus 10 (IQR 8-11) days (p < 0.001) for L- versus O-CRS/HIPEC. Despite a normal pre-operative CT scan, 13/55 (23.6%) L-CRS/HIPEC patients had acellular mucin and 2/55 (3.5%) had mucin with epithelium present in their specimens. Residual appendix tumour was identified in 2/55 patients (3.6%). Clavien-Dindo Grade 1-4 complications were similar in both groups with no mortality.

Conclusions:

L-CRS/HIPEC for LAMN II takes longer; however patients have significantly reduced length of HDU and overall stay, without increased post-operative complications. A significant proportion of LAMN II patients undergoing L-CRS/HIPEC have extra-appendiceal acellular mucin with some cases demonstrating residual cellular epithelium from the LAMN II. The risk of these patients developing PMP without surgery is under current review.

Eur J Cancer. 2020 Mar;127:76-95. doi: 10.1016/j.ejca.2019.10.034. Epub 2020 Jan 24.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review

Authors:

Auer RC1, Sivajohanathan D2, Biagi J3, Conner J4, Kennedy E5, May T6


Abstract:

The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs. If no RCTs were identified, prospective and retrospecctive comparative studies (where confounders are controlled for studies with greater than 30 patients) were included. Overall survival, progression-free survival, recurrence-free survival, adverse events and quality of life data were extracted. For patients with newly diagnosed, primary stage III epithelial ovarian, fallopian tube or primary peritoneal carcinoma, HIPEC with CRS should be considered for those with at least stable disease following neoadjuvant chemotherapy at the time of interval CRS if complete or optimal cytoreduction is achieved. There is insufficient evidence to recommend the addition of HIPEC when primary CRS is performed for patients with newly diagnosed, primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma or in those with recurrent ovarian cancer outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of peritoneal colorectal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of gastric peritoneal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS in patients with malignant peritoneal mesothelioma or in those with disseminated mucinous neoplasm in the appendix as a standard of care; however, these patients should be referred to HIPEC specialty centres for assessment for treatment as part of an ongoing research protocol.

Eur J Surg Oncol. 2020 Jan 17. pii: S0748-7983(20)30021-4. doi: 10.1016/j.ejso.2020.01.020. [Epub ahead of print]

Cost analysis of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and the risk factors for their increased cost in a public insurance health care system - Single centre study

Authors:

Klos D1, Riško J1, Kriváčková D1, Loveček M1, Skalický P1, Neoral Č1, Melichar B2, Mohelníková-Duchoňová B3, Lemstrová R4


Abstract

Introduction:

This study aimed to evaluate the costs of CRS and HIPEC and treatment of the related postoperative complications in the public healthcare system. We also aimed to identify the risk factors that increase the cost of CRS and HIPEC.

Materials and Methods:

We retrospectively evaluated 80 patients who underwent CRS and HIPEC between February 2016 and November 2018 in the Department of Surgery, University Hospital of Olomouc, Czech Republic. Intraoperative factors and postoperative complications were assessed. The treatment cost included the surgery, hospital stay, intensive care unit (ICU) admission, pharmaceutical charges including medication, hospital supplies, pathology, imaging, and allied healthcare services.

Results:

The postoperative morbidity rate was 50%, and the mortality rate was 2.5%. The mean length of hospitalisation and ICU admission was 15.44 ± 8.43 and 6.15 ± 4.12 for all 80 patients and 10.73 ± 2.93 and 3.73 ± 1.32, respectively, for 40 patients without complications, and 20.15 ± 13.93 and 8.58 ± 6.92, respectively, for 40 patients with complications. The total treatment cost reached €606,358, but the total reimbursement was €262,931; thus, the CRS and HIPEC profit margin was €-343,427. Multivariate analysis showed that blood loss ≥1.000 ml (p = 0.03) and grade I-V Clavien-Dindo complications (p < 0.001) were independently associated with increased costs.

Conclusions:

The Czech public health insurance system does not fully compensate for the costs of CRS and HIPEC. Hospital losses remain the main limiting factor for further improving these procedures. Furthermore, treatment costs increase with increasing severity of postoperative complications

Ann Surg Oncol. 2020 Jan 24. doi: 10.1245/s10434-020-08210-5. [Epub ahead of print]

Prognostic Molecular Classification of Appendiceal Mucinous Neoplasms Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Authors:

Su J1, Jin G2, Votanopoulos KI3, Craddock L2, Shen P3, Chou JW1, Qasem S4, O'Neill SS4, Perry KC3, Miller LD5,6, Levine EA7


Abstract

Background:

Appendiceal mucinous neoplasm (AMN) with peritoneal metastasis is a rare but deadly disease with few prognostic or therapy-predictive biomarkers to guide treatment decisions. Here, we investigated the prognostic and biological attributes of gene expression-based AMN molecular subtypes.

Methods:

AMN specimens (n = 138) derived from a population-based subseries of patients treated at our institution with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 05/2000 and 05/2013 were analyzed for gene expression using a custom-designed NanoString 148-gene panel. Signed non-negative matrix factorization (sNMF) was used to define a gene signature capable of delineating robustly-classified AMN molecular subtypes. The sNMF class assignments were evaluated by topology learning, reverse-graph embedding and cross-cohort performance analysis.

Results:

Three molecular subtypes of AMN were discerned by the expression patterns of 17 genes with roles in cancer progression or anti-tumor immunity. Tumor subtype assignments were confirmed by topology learning. AMN subtypes were termed immune-enriched (IE), oncogene-enriched (OE) and mixed (M) as evidenced by their gene expression patterns, and exhibited significantly different post-treatment survival outcomes. Genes with specialized immune functions, including markers of T-cells, natural killer cells, B-cells, and cytolytic activity showed increased expression in the low-risk IE subtype, while genes implicated in the promotion of cancer growth and progression were more highly expressed in the high-risk OE subtype. In multivariate analysis, the subtypes demonstrated independent prediction power for post-treatment survival.

Conclusions:

Our findings suggest a greater role for the immune system in AMN than previously recognized. AMN subtypes may have clinical utility for predicting CRS/HIPEC treatment outcomes.

Eur J Surg Oncol. 2020 Jan 15. pii: S0748-7983(20)30022-6. doi: 10.1016/j.ejso.2020.01.017. [Epub ahead of print]

Perioperative safety after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal origin: Experience on 254 patients from a single center

Authors:

Li XB1, Ma R2, Ji ZH3, Lin YL4, Zhang J5, Yang ZR6, Chen LF7, Yan FC8, Li Y9


Abstract

Objective:

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a standard treatment for pseudomyxoma peritonei (PMP) recommended by Peritoneal Surface Oncology Group International (PSOGI). The study is to analyze the incidence of perioperative serious adverse events (SAEs) of CRS + HIPEC to treat PMP patients, and identify the risk factors, for guiding the prevention of SAEs.

Methods:

This is a retrospective study on the PMP database established at our center. The clinicopathological features, treatment details and SAEs information on the PMP patients are systematically established in this database. The incidence, organ system distribution and severity of perioperative SAEs are analyzed. Univariate and multivariate analyses are performed to identify the independent risk factors.

Results:

Among the 272 CRS + HIPEC procedures for 254 PMP patients, there are 93 (34.2%) SAEs. Six systems are involved in the SAEs, including infections (9.6%), digestive system (8.1%), respiratory system (6.3%), cardiovascular system (5.5%), hematological system (2.9%), and urinary system (1.5%), in terms of frequency. In terms of severity, the majority is grade III SAEs (27.9%), followed by grade IV SAEs (4.8%) and grade V SAEs (1.5%). Univariate analysis reveals 4 risk factors for perioperative SAEs: HIPEC regimens (P = 0.020), PCI (P = 0.025), intraoperative red blood cell transfusion volume (P = 0.004), and intraoperative blood loss volume (P = 0.002). Multivariate and logistic regression model analysis identifies only one independent risk factor for perioperative SAEs: intraoperative blood loss volume (P = 0.001, OR = 0.344, 95%CI: 0.182-0.649).

Conclusions:

PMP patients treated by CRS + HIPEC at experienced centers could have acceptable safety. Improving the surgical techniques and developing the integrated hemostasis techniques are essential to reduce intraoperative blood loss and decrease SAEs rate.

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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Podręcznik „Pierwotne i wtórne nowotwory otrzewnej. Diagnostyka. Leczenie.”

okładka ksiązki „Pierwotne i wtórne nowotwory otrzewnej. Diagnostyka. Leczenie.”

Podręcznik został napisany przez doświadczonych chirurgów i lekarzy innych specjalności, wykonujących zabiegi cytoredukcyjne w nowotworach otrzewnej w jednym z najlepszych ośrodków na świecie – Peritoneal Malignancy Institute w Basingstoke w Wielkiej Brytanii. Ich wiedza i doświadczenie w leczeniu chorych z pierwotnymi i wtórnymi nowotworami otrzewnej zaowocowała wypracowaniem standardów postępowania i techniką operacyjną godnymi naśladowania.

Pierwsza polska monografia „Terapia CRS + HIPEC”

okładka ksiązki „Terapia CRS + HIPEC”

Książka wydana została jako 9. tom serii Biblioteka Chirurga Onkologa. Profesorowie Tomasz Jastrzębski i Wojciech Polkowski, pionierzy techniki CRS + HIPEC w Polsce, wraz z zespołem współautorów, wysokiej klasy specjalistów, opisują najnowsze możliwości leczenia chorych z przerzutami nowotworu do otrzewnej.

Ośrodki wykonujące zabiegi cytoredukcyjne HIPEC:

Ośrodek Leczenia Nowotworów Otrzewnej
Uniwersyteckie Centrum Kliniczne w Gdańsku

Kod ośrodka GDA
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 I
Dolnąśląskie Centrum Onkologii we Wrocławiu

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

Klinika Chirurgii Ogólnej, Onkologicznej i Gastroenterologicznej
Szpital Uniwersytecki w Krakowie

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

Klinika Chirurgii Onkologicznej
Centrum Onkologii – Bydgoszcz

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

Klinika Gastroenterologii Onkologicznej
Narodowy Instytut Onkologii
im. Marii Skłodowskiej - Curie

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

Klinika Ginekologii Onkologicznej
Narodowy Instytut Onkologii
im. Marii Skłodowskiej - Curie

Kod ośrodka WAB
02-781 Warszawa
ul. Roentgena 5
prof dr hab med. Mariusz Bidziński
tel 22 546 22 95, 501 699 799

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

Klinika Chirurgii Onkologicznej
Uniwersytet Medyczny w Lublinie

Kod ośrodka LUB
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
Wojewódzkie Wielospecjalistyczne
Centrum Onkologii i Traumatologii
im. M.Kopernika w Łodzi

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

Klinika Chirurgii i Urologii Dzieci i Młodzieży
COPERNICUS Podmiot Leczniczy

Kod ośrodka GDZ
80-803 Gdańsk
ul. Nowe Ogrody 1-6
prof. dr hab med Piotr Czauderna
tel.: 58 764 01 90 (Sekretariat)