HITHOC in 2018 – Where are we now?

We’ve come along way when discussing Mesothelioma and the use of hyperthermic  intrathoracic chemotherapy (HITHOC) since this site was started back in 2010.  In fact, for our first discussions about this technique, we had to travel to Ganziantep, Turkey

Back then, Dr. Isik was one of very few researchers to be actively looking, investigating and performing research in this area.  So, when thoracics.org wanted to report about HITHOC – we had to go to the source.   There were a few other researchers, in scattered locations across the globe, such as the Nara experiment in Japan, a couple of case reports out of Germany, but otherwise, it was a barren landscape in thoracic research.

Then came Dr. Marcello Migliore and the Italian research teams..  and then everyone else.  HITHOC has expanded from the treatment of malignant pleural mesothelioma to a viable treatment for malignant pleural effusions from almost any kind of primary cancer (including lung, breast, thymoma).

So now that Thoracics.org is preparing to return to Italy for VATS International 2018 – it’s time to check in one the state of HITHOC in 2018.


It seems the Germans have the answer.  Unfortunately, they are keeping it to themselves, because Reid et. al’s most recent article that sums up state of HITHOC in over 116 German institutions is published only in german.  Thoracics.org has attempted to contact the lead author for more details, but at the time of this publication, we are still awaiting a reply.

 The English version abstract gives us a tiny sliver – of the results of the authors survey of german thoracic surgery practices.  Ried et al. reports that of the 116 facilities they surveyed, 17 thoracic surgery departments in Germany are performing HITHOC.  All of these facilities perform HITHOC for malignant pleural mesothelioma, with 11 facilities including patients with thymoma with pleural metastasis.  Only 7 facilities report performing HITHOC on patients with other secondary pleural carcinosis.  While the inclusion criteria doesn’t appear to be the same throughout Germany, the procedural protocol appears to be fairly universal – hyperthermic (42 centigrade) application of cisplatin or cisplatin combinations for a 60 minute cycle.  But that tiny scrap of an abstract still leaves thoracics.org with so many questions.  Enough in fact, that we promise the authors their own feature article, if we get a reply.


Migliore’s recent editorial, while interesting, doesn’t really add much to our current landscape.   On the thoracics.org wishlist instead is a more step-by-step discussion of the Catania University thoracic surgery department’s HITHOC treatment algoriths and review of research results.

Luzzi et al. out of Siena, Italy published a small-scale study on the physiologic effects of HITHOC after pleurectomy and decortication.  Notably, these patients are undergoing an more extensive operation than HITHOC alone, and there are part of a smaller subset of patients with a more aggressive cancer than some of our other studies, namely malignant pleural mesothelioma (MPM).  While the authors followed 41 patients undergoing HITHOC at their facility, only ten patients were enrolled in their study looking at hemodynamics.

This study which included 10 patients, looked at the hemodynamics of patients before, during the HITHOC procedure, and the early post-operative procedure.  The authors were trying to address possible causes of the high rate of complications cited in previous researchers studies.  These studies also showed that adequate fluid hydration intra-operatively reduced many of these complications such as hypotension and acute renal injury.  The authors hypothesized that microvascular changes (namely systemic vasodilation and with a capillary leak syndrome) contributed to the development of these operative complications.  They used both vasopressors and specific fluid volume resuscitation recipes to reduce these microvascular changes during and after the procedure but also observed that colloid and blood transfusions had similar effects.   The authors call for the adoption of hemodyanamic monitoring parameters similar to those used in cardiac surgery (Swan Ganz, SvO2 monitoring) for better detection and treatment of these microvascular changes to limit the development of complications.


Chinese authors offer us the most comprehensive view of HITHOC up-to-date.  Not through newly published results or an original work, but through a comprehensive meta-analysis of previously published works.  Zhou et. al do a nice job of reviewing the existing research and discussing the different applications of HITHOC (outside of malignant pleural mesothelioma for malignant pleural effusions of any underlying etiology.  Unfortunately, Thoracics.org has covered many of these articles before – so while it’s a good overview article for HITHOC novices, long-term readers already know the in-depth details of the Isik study,  Zhang’s results, and several of the other major studies discussed in Zhou et. al.  But the authors make a very salient point – that while several of the programs have formalized and standardized HITHOC protocols, these protocols often differ from hospital to hospital, with no set universal chemotherapeutic regimen in place.  A universal protocol would make it easier to conduct additional meta-analyses and RCTs to determine if HITHOC for malignant pleural effusions are as promising as they appear to be.  A HITHOC registry, anyone?



Luzzi, et. al. (2018). Hyperthermic intrathoracic chemotherapy after extended pleurectomy and decortication for malignant pleural mesothelioma: an observational study on outcome and microcirculatory changes.   Journal of thoracic disease, vol 10, supp 2.

Migliore, M. (2017). Debulking surgery and hyperthermic intrathoracic chemotherapy (HITHOC) for lung cancer.  Chinese Journal of Cancer Research, 2017, Dec; 29 (6): 533-534.  Editorial.

Reid, M., Hofmann, H. S., Dienemann, H. & Eichorn, M. (2018).  Implementation of hyperthermic intrathoracic chemotherapy in Germany.  [article in german]. Zentralbl Chir. 2018 Jun, 143 (3): 301-306.  Ried et al. are also the authors of that 2014 article, we discussed in a previous post about anesthesia during HITHOC.

Zhou et. al. (2017).  Effect of hyperthermic intrathoracic chemotherapy on the malignant pleural effusion.  Medicine, 96:1.


*Thoracics.org has a particular interest in the area of HITHOC.  Researchers and HITHOC programs are always invited to submit research,  and other materials for for review here at Thoracics.org 

Author: K Eckland

World of Thoracic Surgery is a blog about the work, research, and practices of thoracic surgeons around the world. It includes case studies, [sometimes] dry research, interviews with thoracic surgeons along with patient perspectives, and feedback.

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