Dr. Fernando Arias

the meat and potatoes of HIPEC

So I have returned to the United States and back on assignment for the next couple of months, so it’s time to get down to business.

A couple of new HIPEC articles came out – which I thought readers might enjoy.  For lighter fare, we will start with an article from the Vancouver Sun.

The first article, by Erin Ellis of the Vancouver Sun, is a Canadian fluff piece complete with sensationalistic headlines and dramatic patient interviews designed to draw attention to Vancouver General Hospital’s new HIPEC program.

 Dr. Fernando Arias

Dr. Fernando Arias, Chief of the HIPEC program at Santa Fe de Bogotá

Now for the meat and potatoes

The second article, which is more academically and scientifically based, is  focused on a study presented at the Southern Surgical Association  in December by Levine, et. al. (2014) “Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1,000 Patients” looks at long-term survival with HIPEC in patients with disseminated peritoneal malignancies.  This study is remarkable for both the duration of the prospective study (which began in 1991) and the large amount of participants for a single site study.  The vast majority of patients enrolled in this study had appendiceal cancer as their primary, but the study also included patients with ovarian, gastric, mesothelioma and colorectal cancers.

The evolution of the procedure and institutional experience led to improved outcomes and reduced complications over the course of the study.  Part of this was due to the development of better patient selection criteria.

This information comes as a ray of hope for patients with these diagnoses and previously given only dismal prognoses.

Dr. Edward Levine, the primary investigator, is the Chief of Surgical Oncology and Director of the Comprehensive Cancer Center at Wake Forest Medical Center in North Carolina.

It was published in the Journal of the American College of Surgeons, and summarized here, at Heme/Onc Today

Levine, et. al. (2014).  Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1,000 Patients.  Journal of the American College of Surgeons, 218(4): 573–585 (April 2014).  No free text available.

Additional HIPEC posts: the HIPEC archives 

HIPEC hits its stride

When I first started reading and writing about HIPEC (after meeting Dr. Arias in Bogota), I was met with a lot of skepticism and sometimes even ridicule, primarily from American physicians.

Several of them derided HIPEC with a vehemence that was unexpected – a vigor that was quite surprising and almost venomous in nature.  I was accused of being ignorant, or more maliciously, a possible fraud or trickster – even when I explained my sources (scientific and medical journals) and reminded critics that I was on a fact-finding mission, not a sales pitch.

I don’t sell HIPEC.  I don’t sell any medical equipment, treatment, or procedures. I don’t market or sell surgeons.  About the only thing I sell  is the occasional copy of one of my books.

No – I don’t sell much.  Instead, I write, I research and I do my best to provide information, and resources to people who are interested in the same topics.  As a healthcare provider, my reasons for writing about these topics may very well differ from my readers – but that’s more perspective than anything else.

When it comes to HIPEC – I was attracted because HIPEC offers hope.  Not in a wild, faith-healing, magic pill , “100% absolutely guaranteed, for positively everyone” kind of way, but in a quiet, evolving medicine kind of way.. Meaning that we are still learning about it -and who it can help..

So it was disappointing to have that hope dimmed by other medical professionals, but then – sometimes procedures and treatments that sound promising DO end up disappointing.  So I’ve kept an eye on the research, and kept reading..

It’s been a on-going process.. Imagine my delight to see that over SIXTY articles have been published in medical & research journals on HIPEC in just the last six months.. Some with great results, some okay, – some detailing complications..

(I’ve posted some of the citations here).  Most of the articles aren’t free but there is a notation to the ones that are.

1. Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies.
  Işık AF, Sanlı M, Yılmaz M, Meteroğlu F, Dikensoy O, Sevinç A, Camcı C, Tunçözgür B, Elbeyli L.
  Respir Med. 2013 May;107(5):762-7. doi: 10.1016/j.rmed.2013.01.010. Epub 2013 Feb 23.
  PMID: 23462236 [PubMed – in process]  This is actually HITHOC
  Related citations
2. Patients at risk for peritoneal surface malignancy of colorectal cancer origin: the role of second look laparotomy.
  Brücher B, Stojadinovic A, Bilchik A, Protic M, Daumer M, Nissan A, Itzhak A.
  J Cancer. 2013;4(3):262-9. doi: 10.7150/jca.5831. Epub 2013 Mar 15.
  PMID: 23459716 [PubMed] Free PMC Article
  Related citations
3. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis (HIPEC): the Danish experience.
  Iversen LH, Rasmussen PC, Hagemann-Madsen R, Laurberg S.
  Colorectal Dis. 2013 Mar 4. doi: 10.1111/codi.12185. [Epub ahead of print]
  PMID: 23458368 [PubMed – as supplied by publisher]
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4. Complications and toxicities after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
  Canda AE, Sokmen S, Terzi C, Arslan C, Oztop I, Karabulut B, Ozzeybek D, Sarioglu S, Fuzun M.
  Ann Surg Oncol. 2013 Apr;20(4):1082-7. doi: 10.1245/s10434-012-2853-x. Epub 2013 Mar 2.
  PMID: 23456387 [PubMed – in process]
  Related citations
5. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
  Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S.
  Ann Surg Oncol. 2013 Apr;20(4):1093-100. doi: 10.1245/s10434-012-2845-x. Epub 2013 Mar 2.
  PMID: 23456386 [PubMed – in process]
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6. Extensive cytoreductive surgery for appendiceal carcinomatosis: morbidity, mortality, and survival.
  Wagner PL, Austin F, Maduekwe U, Mavanur A, Ramalingam L, Jones HL, Holtzman MP, Ahrendt SA, Zureikat AH, Pingpank JF, Zeh HJ, Bartlett DL, Choudry HA.
  Ann Surg Oncol. 2013 Apr;20(4):1056-62. doi: 10.1245/s10434-012-2791-7. Epub 2013 Mar 2.
  PMID: 23456385 [PubMed – in process]
  Related citations
7. Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy.
  Leinwand JC, Bates GE, Allendorf JD, Chabot JA, Lewin SN, Taub RN.
  Ann Surg Oncol. 2013 Apr;20(4):1101-4. doi: 10.1245/s10434-012-2790-8. Epub 2013 Mar 2.
  PMID: 23456384 [PubMed – in process] Free PMC Article
  Related citations
8. Assessment of neoadjuvant chemotherapy on operative parameters and outcome in patients with peritoneal dissemination from high-grade appendiceal cancer.
  Turner KM, Hanna NN, Zhu Y, Jain A, Kesmodel SB, Switzer RA, Taylor LM, Richard Alexander H Jr.
  Ann Surg Oncol. 2013 Apr;20(4):1068-73. doi: 10.1245/s10434-012-2789-1. Epub 2013 Mar 2.
  PMID: 23456383 [PubMed – in process]
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9. Surveillance MR imaging is superior to serum tumor markers for detecting early tumor recurrence in patients with appendiceal cancer treated with surgical cytoreduction and HIPEC.
  Low RN, Barone RM, Lee MJ.
  Ann Surg Oncol. 2013 Apr;20(4):1074-81. doi: 10.1245/s10434-012-2788-2. Epub 2013 Mar 2.
  PMID: 23456382 [PubMed – in process]
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10. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from rectal cancer.
  Votanopoulos KI, Swett K, Blackham AU, Ihemelandu C, Shen P, Stewart JH, Levine EA.
  Ann Surg Oncol. 2013 Apr;20(4):1088-92. doi: 10.1245/s10434-012-2787-3. Epub 2013 Mar 2.
  PMID: 23456381 [PubMed – in process]
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11. Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and dissecting effects of hyperthermia.
  Pelz JO, Vetterlein M, Grimmig T, Kerscher AG, Moll E, Lazariotou M, Matthes N, Faber M, Germer CT, Waaga-Gasser AM, Gasser M.
  Ann Surg Oncol. 2013 Apr;20(4):1105-13. doi: 10.1245/s10434-012-2784-6. Epub 2013 Mar 2.
  PMID: 23456378 [PubMed – in process]
  Related citations
12. Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies.
  Königsrainer I, Horvath P, Struller F, Forkl V, Königsrainer A, Beckert S.
  Langenbecks Arch Surg. 2013 Jun;398(5):745-9. doi: 10.1007/s00423-013-1065-6. Epub 2013 Mar 1.
  PMID: 23456355 [PubMed – in process]
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13. Assessment of clinical benefit and quality of life in patients undergoing cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for management of peritoneal metastases.
  Zhu Y, Hanna N, Boutros C, Alexander HR Jr.
  J Gastrointest Oncol. 2013 Mar;4(1):62-71. doi: 10.3978/j.issn.2078-6891.2012.053.
  PMID: 23450068 [PubMed] Free PMC Article
  Related citations
14. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for palliative treatment of malignant ascites from gastrointestinal stromal tumours.
  Ong E, Diven C, Abrams A, Lee E, Mahadevan D.
  J Palliat Care. 2012 Winter;28(4):293-6. No abstract available.
  PMID: 23413766 [PubMed – indexed for MEDLINE]
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15. A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial.
  Glockzin G, Rochon J, Arnold D, Lang SA, Klebl F, Zeman F, Koller M, Schlitt HJ, Piso P.
  BMC Cancer. 2013 Feb 7;13:67. doi: 10.1186/1471-2407-13-67.
  PMID: 23391248 [PubMed – in process] Free PMC Article
  Related citations
16. Heated intraperitoneal chemotherapy in appendiceal cancer treatment.
  Cianos R, Lafever S, Mills N.
  Clin J Oncol Nurs. 2013 Feb;17(1):84-7, 90. doi: 10.1188/13.CJON.84-87.
  PMID: 23372101 [PubMed – in process]
  Related citations
17. Aggressive locoregional management of recurrent peritoneal sarcomatosis.
  Baumgartner JM, Ahrendt SA, Pingpank JF, Holtzman MP, Ramalingam L, Jones HL, Zureikat AH, Zeh HJ 3rd, Bartlett DL, Choudry HA.
  J Surg Oncol. 2013 Mar;107(4):329-34. doi: 10.1002/jso.23232. Epub 2013 Feb 5.
  PMID: 23386388 [PubMed – indexed for MEDLINE]
  Related citations
18. A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC.
  Harrison LE, Tiesi G, Razavi R, Wang CC.
  Ann Surg Oncol. 2013 Jun;20(6):1843-50. doi: 10.1245/s10434-013-2874-0. Epub 2013 Jan 26.
  PMID: 23354567 [PubMed – in process]
  Related citations
19. Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study.
  Argenta PA, Sueblinvong T, Geller MA, Jonson AL, Downs LS Jr, Carson LF, Ivy JJ, Judson PL.
  Gynecol Oncol. 2013 Apr;129(1):81-5. doi: 10.1016/j.ygyno.2013.01.010. Epub 2013 Jan 23.
  PMID: 23352917 [PubMed – indexed for MEDLINE]
1. Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).
  Mazzei MA, Khader L, Cirigliano A, Cioffi Squitieri N, Guerrini S, Forzoni B, Marrelli D, Roviello F, Mazzei FG, Volterrani L.
  Abdom Imaging. 2013 Jun 7. [Epub ahead of print]
  PMID: 23744439 [PubMed – as supplied by publisher]
  Related citations
2. Cytoreductive surgery and intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis from colorectal origin.
  Losa F, Barrios P, Salazar R, Torres-Melero J, Benavides M, Massuti T, Ramos I, Aranda E.
  Clin Transl Oncol. 2013 Jun 6. [Epub ahead of print]
  PMID: 23740133 [PubMed – as supplied by publisher]
  Related citations
3. Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases.
  Chua TC, Quinn LE, Zhao J, Morris DL.
  J Surg Oncol. 2013 Jun 5. doi: 10.1002/jso.23356. [Epub ahead of print]
  PMID: 23737041 [PubMed – as supplied by publisher]
  Related citations
4. Importance of standardizing the dose in hyperthermic intraperitoneal chemotherapy (HIPEC): a pharmacodynamic point of view.
  Mas-Fuster MI, Ramon-Lopez A, Nalda-Molina R.
  Cancer Chemother Pharmacol. 2013 Jun 5. [Epub ahead of print] No abstract available.
  PMID: 23736155 [PubMed – as supplied by publisher]
  Related citations
5. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma.
  Sun Y, Shen P, Stewart JH, Russell GB, Levine EA.
  Am Surg. 2013 Jun;79(6):644-8.
  PMID: 23711278 [PubMed – in process]
  Related citations
6. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal sarcomatosis.
  Randle RW, Swett KR, Shen P, Stewart JH, Levine EA, Votanopoulos KI.
  Am Surg. 2013 Jun;79(6):620-4.
  PMID: 23711273 [PubMed – in process]
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7. Prognostic Factors of Peritoneal Metastases from Colorectal Cancer following Cytoreductive Surgery and Perioperative Chemotherapy.
  Yonemura Y, Canbay E, Ishibashi H.
  ScientificWorldJournal. 2013 Apr 18;2013:978394. doi: 10.1155/2013/978394. Print 2013.
  PMID: 23710154 [PubMed – in process] Free PMC Article
  Related citations
8. Is there a role for intraperitoneal administration of heparin in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal cancer origin? Current data and future orientations.
  Seretis F, Seretis C.
  Med Hypotheses. 2013 May 13. doi:pii: S0306-9877(13)00221-1. 10.1016/j.mehy.2013.04.040. [Epub ahead of print]
  PMID: 23680001 [PubMed – as supplied by publisher]
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9. The benefit of intraperitoneal chemotherapy for the treatment of colorectal carcinomatosis.
  Francescutti V, Rivera L, Seshadri M, Kim M, Haslinger M, Camoriano M, Attwood K, Kane JM 3rd, Skitzki JJ.
  Oncol Rep. 2013 Jul;30(1):35-42. doi: 10.3892/or.2013.2473. Epub 2013 May 15.
  PMID: 23673557 [PubMed – in process]
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10. Clinical study of cisplatin hyperthermic intraperitoneal perfusion chemotherapy in combination with docetaxel, 5-flourouracil and leucovorin intravenous chemotherapy for the treatment of advanced-stage gastric carcinoma.
  Zhibing W, Qinghua D, Shenglin M, Ke Z, Kan W, Xiadong L, Pengjun Z, Ruzhen Z.
  Hepatogastroenterology. 2013 May 10;60(128). doi: 10.5754/hge13038. [Epub ahead of print]
  PMID: 23598741 [PubMed – as supplied by publisher]
  Related citations
11. Outcome of patients with aggressive pseudomyxoma peritonei treated by cytoreductive surgery and intraperitoneal chemotherapy.
  Arjona-Sanchez A, Muñoz-Casares FC, Casado-Adam A, Sánchez-Hidalgo JM, Ayllon Teran MD, Orti-Rodriguez R, Padial-Aguado AC, Medina-Fernández J, Ortega-Salas R, Pulido-Cortijo G, Gómez-España A, Rufián-Peña S.
  World J Surg. 2013 Jun;37(6):1263-70. doi: 10.1007/s00268-013-2000-2.
  PMID: 23532601 [PubMed – in process]
  Related citations
12. Treatment of peritoneal carcinomatosis from breast cancer by maximal cytoreduction and HIPEC: A preliminary report on 5 cases.
  Cardi M, Sammartino P, Framarino ML, Biacchi D, Cortesi E, Sibio S, Accarpio F, Luciani C, Palazzo A, di Giorgio A.
  Breast. 2013 Mar 21. doi:pii: S0960-9776(13)00053-2. 10.1016/j.breast.2013.02.020. [Epub ahead of print]
  PMID: 23523180 [PubMed – as supplied by publisher]
  Related citations
13. Primary peritoneal serous carcinoma treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. A multi-institutional study of 36 patients.
  Bakrin N, Gilly FN, Baratti D, Bereder JM, Quenet F, Lorimier G, Mohamed F, Elias D, Glehen O; Association Française de Chirurgie.
  Eur J Surg Oncol. 2013 Mar 16. doi:pii: S0748-7983(13)00263-1. 10.1016/j.ejso.2013.02.018. [Epub ahead of print]
  PMID: 23510853 [PubMed – as supplied by publisher]
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14. Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis.
  Kepenekian V, Aloy MT, Magné N, Passot G, Armandy E, Decullier E, Sayag-Beaujard A, Gilly FN, Glehen O, Rodriguez-Lafrasse C.
  Cell Stress Chaperones. 2013 Mar 19. [Epub ahead of print]
  PMID: 23508575 [PubMed – as supplied by publisher]
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15. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Asian Patients: 100 Consecutive Patients in a Single Institution.
  Teo MC, Tan GH, Tham CK, Lim C, Soo KC.
  Ann Surg Oncol. 2013 Mar 17. [Epub ahead of print]
  PMID: 23504144 [PubMed – as supplied by publsh
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16. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma.
  Alexander HR Jr, Bartlett DL, Pingpank JF, Libutti SK, Royal R, Hughes MS, Holtzman M, Hanna N, Turner K, Beresneva T, Zhu Y.
  Surgery. 2013 Jun;153(6):779-86. doi: 10.1016/j.surg.2013.01.001. Epub 2013 Mar 13.
  PMID: 23489943 [PubMed – in process]
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17. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy as salvage treatment for a late wound recurrence of endometrial cancer.
  Santeufemia DA, Lumachi F, Basso SM, Tumolo S, Re GL, Capobianco G, Bertozzi S, Pasqual EM.
  Anticancer Res. 2013 Mar;33(3):1041-4.
  PMID: 23482779 [PubMed – indexed for MEDLINE]
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18. Preoperative carcinoembryonic antigen level predicts prognosis in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
  Canbay E, Ishibashi H, Sako S, Mizumoto A, Hirano M, Ichinose M, Takao N, Yonemura Y.
  World J Surg. 2013 Jun;37(6):1271-6. doi: 10.1007/s00268-013-1988-7.
  PMID: 23467926 [PubMed – in process]
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19. Rhabdomyolysis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a case report.
  Bielen R, Verswijvel G, Van der Speeten K.
  Case Rep Oncol. 2013 Jan;6(1):36-44. doi: 10.1159/000346471. Epub 2013 Jan 18.
  PMID: 23467441 [PubMed] Free PMC Article

The HIPEC calculator

We’ve talked a lot about HIPEC here – but we have not really talked about the risks of treatment.  While we mentioned the arduous nature of the procedure itself, we’ve left more in-depth discussions to the oncologists.

Now researchers at the National Institute of Health have developed a tool to help clinicians and their patients determine the risks of HIPEC.  In an article published over at Surviving Mesothelioma, the authors discuss their recent study and the results.  Since the procedure itself carries significant mortality – the calculator offers an important tool for determining who the best candidates are for successful treatment with this procedure.

Original Article:

Schaub NP, Alimchandani M, Quezado M, Kalina P, Eberhardt JS, Hughes MS, Beresnev T, Hassan R, Bartlett DL, Libutti SK,Pingpank JF, Royal RE, Kammula US, Pandalai P, Phan GQ, Stojadinovic A, Rudloff U, Alexander HR, Avital I. (2012).  A Novel Nomogram for Peritoneal Mesothelioma Predicts Survival.  Ann Surg Oncol. 2012 Dec 12

HIPEC in the news again..

Another story about bringing HIPEC to the masses – this time in Mumbai, India..  I have to wonder about the research for the article – everytime I see the phrase, “A ray of hope”..  sounds suspiciously like the original title of a certain article (in Colombia Reports.com) all of us are familiar with over here at Bogota Surgery.org.

HIPEC and peritoneal mesothelioma – more effective in women?