Tag: Dr. Marcello Migliore

Migliore et al. present final results of pilot study Pleurectomy/ Decortication with HITHOC versus VATS pleurodesis. P.S. – here comes the MARS 2 trial results..

We are here with the latest HITHOC pilot study updates from Dr. Migliore et al. If you remember, Dr. Migliore and his colleagues in Sicily have been investigating and researching the effectiveness of HITHOC for well over a decade. In fact, we’ve talked about this study before, when we presented preliminary findings.  But now the authors are presenting the results of a six-year pilot study with long-term follow-up in a paper that was published in the scientific journal, Cell. (Original paper here).

Why this is important

In the general population, patients diagnosed with malignant pleural mesothelioma (MPM) have a mean survival of 9 to 12 months.  

The mean age at time of death was 70, meaning this disease affects relatively young patients after a long incubation period.  It affects men at a ratio of almost 4 men (3.6)  to one woman. (Presumably, this is related to occupational/ industrial exposures and trends – few women work/ worked in shipyards, construction).

While many people think that asbestos related mesothelioma is a thing of the past (or time limited due to the fact it has known carcinogenic effects), it is still being used in many products in several countries including the United States.  

How do we treat Pleural Mesothelioma now?

Despite this, the standard of treatment is generally palliative in nature.  Talc Pleurodesis is used to drain existing fluid around the lung, and then the talc is used as a sclerosing (or scarring) agent to prevent the pleural surfaces from being able to secrete more fluid. This makes the patient feel better because they breathe better – which is a very important consideration for patient care – but does nothing to treat the underlying cancer or prevent its spread. Patients generally live around 14 months after this procedure, when it is performed for mesothelioma.

Other surgical treatments have been tried in the past including Extrapleural pneumonectomy (EPP), which has a high mortality rate, and Pleurectomy/ Decortication.

Pleurectomy / Decortication, which has replaced EPP in many cases, has a low surgical mortality (1.8%), but carries a high risk of recurrence, meaning many patients’ cancer will return.   The average survival for patients having this procedure is only 17 months.

In contrast, there have been several small studies that suggest that HITHOC offers greater survival for patients with mesotheliomas – with the average survival of 20 to 35 months. But these studies have been small, and many thoracic surgeons and oncologists remain unaware of HITHOC as a potential treatment option. Others remain skeptical of its potential benefits (which is not necessarily a bad thing!) So, Dr. Migliore and his colleagues designed this study to see if a larger scale trial with more participants would be feasible or worthwhile.

Pilot studies like this one are used to determine how many patients need to be enrolled to see a statistically meaningful result, and if there is a “meaningful” result at all.

This is important because many of the studies mentioned in general media do not meet this criteria but are widely reported as successful nonetheless just because of so-called ‘newsworthiness’.  Every time readers see a story on a seemingly miraculous cure based on a garden variety supplement for a wide host of medical problems (depression, arthritis, heart disease, Alzheimer’s or you name it), this is an example why pilot studies are needed to both protect the public and to advance medicine using scientific evidence. (We’ve talked about this before.)

So what does this pilot study show?

As you may recall, the preliminary results from this study, (as we reported in 2021) showed favorable results in the HITHOC treatment group, with improved survival rates, despite the fact that many of the patients that were randomized into the HITHOC treatment group actually had more advanced cancers.

The final data confirms this with 30% of the HITHOC patients (4 out of 13) alive at median follow up of 28 months. (Compared to the pleurodesis group which only had one patient (out of 14) still alive at 19 months.  For the full results of this trial – please see the original article.

The biggest limitation for the researchers in this trial was recruiting patients for enrollment. They reached out to multiple medical centers and oncology practices – and received referrals for only five patients a year, despite the fact that Biancavilla, in Sicily is one of the mesothelioma hotspots. This small number met the threshold for statistical significance for a pilot study – but falls far short of what would be needed for a larger, more powerful study.

but for large scale, multi-site international trials in the future, we need to do a better job at connecting eligible patients with research studies..

Now what? What’s next ?

Now as we wait to see if other surgeons and oncologists will answer the challenge – and participate in a larger, multi-center (international) randomized control trial with hundreds, if not thousands of patients, to compare HITHOC to other treatments. When, and if, that happens, I will report enrollment information for potential referring physicians and patients.

Other news in the treatment of MPM

In the meantime, we await further results from the MARS2 trial, headed by the dynamic Dr. Eric Lim, in the UK. These results will be presented in Singapore, this fall.

The MARS2 trial, unfortunately, doesn’t use any HITHOC protocols but looks at whether pleurectomy/ decortication in addition to chemotherapy alone enhances survival and quality of life.  Now, if only Dr. Lim would introduce some of that chemotherapy (preferably Cisplatin) at 42.5 degrees into the chest cavity. Then we’d really have something to talk about!

References/ additional information

Featured article: Migliore et al. (2023). Comparison of video-assisted pleurectomy /decortication surgery plus hyperthermic intra-thoracic chemotherapy with VATS pleurodesis for treatment of Malignant Pleural Mesothelioma: a pilot study. Cell, 25 May 2023.

Marinaccio et al. (2015). Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues. Occup Environ Med 2015 Sep;72(9):648-55. doi: 10.1136/oemed-2014-102297. Epub 2015 Jun 4.

Nuyts, et al. (2018) Hotspots of Malignant Pleural Mesothelioma in Western Europe. Transl Lung Cancer Res. 2018 Oct; 7(5): 516–519.

As we’ve talked about in a previous interview with Dr. Isik, (Turkiye) there are regional areas where natural conditions (such as asbestos in the soil) lead to mesothelioma clusters. There are also areas, like the naval shipyards in the United States, where occupational/ industrial exposure leads to disease clusters.  In this investigation of mesothelioma clusters in Western Europe, the majority were industrial/ occupational in nature.

Is asbestos illegal?,  The Mesothelioma Center, consumer information by lawyers for mesothelioma patients.

Banning Asbestos,  Mesothelioma.com,  consumer information by lawyers for mesothelioma patients.

Palliative versus curative care in Mesothelioma Mesotheliomafund.com – another legal site for mesothelioma patients.

HITHOC in Germany, a tale of two cities.  Thoracics.org

Guest post: Report from the 3rd Mediterranean Symposium in Thoracic Surgical Oncology – VATS

An invited report from Dr. Marcello Migliore on the recent Italian conference on VATS and lung cancer


 Report from the 3rd Mediterranean Symposium in Thoracic Surgical Oncology on VATS RESECTIONS FOR LUNG CANCER: moving toward standard of care.

Speakers and moderators at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology
Speakers and moderators at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology

 The third mediterranean symposium on thoracic surgical oncology was  successful.  The symposium was held the 21st – 22nd april 2016  at the Aula Magna of the Faculty of Medicine at the University of Catania. More than 150 people attended, and among them there were thoracic surgeons, general surgeons, oncologists, chest physicians, residents and medical students.  This year, we had speakers from Europe and the USA.  The main topic was VATS resections for lung cancer (Photo 1). During the opening ceremony, the Rector Giacomo Pignataro awarded a medal to Professor Tom Treasure for enhancing our outstanding education and research experience (Photo 2).

Photo 2: The Rector of the University of Catania  is giving the medal to Professor Tom Treasure
Photo 2: The Rector of the University of Catania  is giving the medal to Professor Tom Treasure

Although the concept of operating thru a small port was born and developed in Europe (1- 7) it has been noted that 90% of papers on uniportal VATS lobectomy come from East Asian countries (8-11).  Throughout the symposium  different speakers agreed that a  proper definition of uniportal VATS is mandatory to speak the same language worldwide.

Awake thoracic surgery was discussed together with the need of accurate  preoperative staging procedures such as endobronchial ultrasound, videomediastinoscopy or Video-assisted mediastinal lympadenectomy.   It was concluded that a wide spectrum of factors must be considered when determining the appropriate tests to assess the lymph nodes in  NSCLC, which includes not only the sensitivity and specificity of the test,  but also the ability to perform  the procedure on an individual patient.

Data from New York showed very clearly that there have been no large-scale randomized control trials to compare open and VATS lobectomy. Although most may agree with the short-term superiority of VATs lobectomy over its open counterpart, many argue that is an in adequate oncologic procedure. Hence whether the approach is equivalent in overall and cancer specific survival to its open counterpart is not known. He also reported an important recent analysis of SEER-Medicare which confirmed that VATS lobectomy appears to have similar survival to its open counterparts (12).

A magnificent video was presented to explain every step of the lobectomies performed through a small skin incision.  A long discussion followed and all auditorium proposed that ‘single incision’ VATS probably define better than uniportal VATS what surgeons are doing worldwide. Certainly the length of skin incision is important and should be taken in serious consideration.  We felt that a consensus conference is probably necessary  consensus conference is probably necessary.  The indication for a Wedge resection rather than lobectomy in initial stage lung cancer is still weak.

The Italian VATS group was formed in 2013 , and nowadays there are 65 participating centres and that 2800 VATS lobectomy have already been included. In Catania we joined the group few months ago (13)

A very interesting session for juniors and medical students from UK and Italy was carried out,  and 12 abstracts have been presented as interactive posters.  Two of them have been chosen for possible publication in Future Oncology.

Finally, the first data survival seems to benefit little from the various even growing “personal” modifications of the standard VATS technique. Since there is a limited variation between VATS and uniportal VATS, the likelihood is that either VATS and uniportal VATS will be operative in the near future. Its success will depend on survival advantages and decrease chest pain  and not just on new technical instrumentation. To protect patient’s safety, the length  of the skin incision should  be chosen on the basis of several clinical factors and not in relation of modern “demand”.  Although the trial VIOLET is ongoing in UK to demonstrate if VATS resection for lung cancer is better than open thoracotomy, doubts arises  as standard postero-lateral thoracotomy for lung cancer seems to be an incision which is performed rarely today.  A skin incision of 6-8 cm (mini-thoracotomy) with video assistance is enough for most of lung resections. The question which arises is if a mini-thoracotomy of 6 cm should be called “uniportal” or not.

Marcello Migliore, MD

Thoracic surgeon and invited commentator

Dr. Marcello Migliore
Dr. Marcello Migliore

  1. Migliore M Initial History of Uniportal Video-Assisted Thoracoscopic Surgery. Ann Thorac Surg 2016;101 (1), 412-3.
  2. Migliore M, Calvo D, Criscione A, Borrata F. Uniportal video assisted thoracic surgery: summary of experience, mini-review and perspectives. Journal of Thoracic Disease 2015; 7 (9), E378-E380
  3. Migliore, M., Giuliano, R., & Deodato, G. (2000). Video assisted thoracic surgery through a single port. In Thoracic Surgery and Interdisciplinary Symposium on the threshold of the Third Millennium. An International Continuing Medical Education Programme. Naples, Italy (pp. 29-30).
  4. Migliore, M., Deodato, G. (2001). A single-trocar technique for minimally invasive surgery of the chest. Surgical Endoscopy, 8(15), 899-901.
  5. Migliore M. Efficacy and safety of single-trocar technique for minimally invasive surgery of the chest in the treatment of noncomplex pleural disease. J Thorac Cardiovasc Surg 2003;126:1618-23.
  6. Rocco, G., Martin-Ucar, A., & Passera, E. (2004). Uniportal VATS wedge pulmonary resections. The Annals of Thoracic Surgery, 77(2), 726-728.
  7. Gonzalez D, Paradela M, Garcia J, et al. Single-port video-assisted thoracoscopic lobectomy. Interact Cardiovasc Thorac Surg 2011;12:514-5.
  8. Yang HC, Noh D. Single incision thoracoscopic lobectomy through a 2.5 cm skin incision. J Thorac Dis  2015;7:E122-5.
  9. Ocakcioglu I, Sayir F, Dinc M. A 3-cm Single-port Video-assisted Thoracoscopic Lobectomy for Lung Cancer. Surg Laparosc Endosc Percutan Tech 2015;25:351-3.
  10. Kamiyoshihara M, Igai H, Ibe T, et al. A 3.5-cm Single-Incision VATS Anatomical Segmentectomy for Lung Ann Thorac Cardiovasc Surg 2015;21:178-82.
  11. Zhu Y, Xu G, Zheng B, et al. Single-port video-assisted thoracoscopic surgery lung resection: experiences in Fujian Medical University Union Hospital. J Thorac Dis 2015;7:1241-51.
  12. Paul S, Isaacs AJ, Treasure T, Altorki NK, Sedrakyan A. Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database. BMJ 2014;349:g5575
  13. Migliore, M., Criscione, A., Calvo, D., Borrata, F., Gangemi, M., & Attinà, G. (2015). Preliminary experience with video-assisted thoracic surgery lobectomy for lung malignancies: general considerations moving toward standard practice. Future Oncology, 11(24s), 43-46.
  14. Migliore M. Will the widespread use of uniportal surgery influence the need of surgeons ? Postgrad Med J 2016 (in press).