Q and A with Migliore et al.. about Hithoc and Mesothelioma in Catania, Italy

Thoracics.org follows up with Dr. Marcello Migliore from the University of Catania, on his work in the area of HITHOC and malignant pleural mesothelioma

Dr. Migliore and his team performing HITHOC
Dr. Migliore and his team performing HITHOC

As discussed in a previous post on HITHOC and Mesothelioma, Dr. Marcello Migliore and his colleagues in Catania, Italy have published results from a small pilot study on the use of HITHOC (cytoreductive surgery and intrathoracic chemotherapy) to treat malignant pleural mesothelioma.

Thoracics.org contacted Dr. Migliore to find out more about that study as well as his on-going research in this area. He was also kind enough to offer his opinions on Hope and the diagnosis of malignant mesothelioma.

On-going research on HITHOC

Dr. Marcello Migliore
Dr. Marcello Migliore

Thoracics.org: Dr. Migliore, woud you tell us more about your current research on HITHOC and mesothelioma?

Dr. Migliore: We are conduction a pilot study to compare pleurodesis with talc vs HITHOC in mesothelioma patients. Goals are quality of life and survival.

Thoracics.org: How many more patients are you hoping to enroll ?


Dr. Migliore: we hope to enroll at least 12 patients (unfortunately in almost 2 years we enrolled only 6 patients)

Thoracics.org:  Would you tell us more about eligibility criteria?

Dr. Migliore:  All patients with mesothelioma will enter the study protocol except those who cannot undergo surgery for poor performance status.

Thoracics.org:  Would you describe the procedures for our readers?

Dr. Migliore: Talc pleurodesis is performed using the uniportal VATS technique (2 cm skin incision), which is a concept that was introduced  by us already in 1998 (and published in 2001 and 2003).  As you know,  Gonzalez- Rivas  is now well known worldwide for using  the concept of uniportal technique to perform major lung resection. Pleuerectomy and decortication with HITHOC is  performed using the bi-portal VATS technique but with an skin incision of around 8 cm.

Thoracics.org:  In your preliminary paper on your last pilot study, there were a couple patients with lung cancer who were included in the HITHOC trials.  Is that the same for your current study?

Dr. Migliore:  While I feel that some patients with lung cancer could have benefited from HITHOC, for this study, the indications must be strictly limited [to patients with malignant mesothelioma only].

As you know, the largest group of patients with lung cancer are patients with more advanced cancer; stage IV lung cancer patients, and because survival  is dismal, the standard practice is no surgery except palliative procedures. But, there are selected patients in whom there is some evidence that surgery could help. For this reason my personal reaction is that,  in the near future, we should aim to prolong survival in stage IV lung cancer patients also by surgery. We are in mind to start a new study on the role of surgery in selected stage IV lung cancer patients.

Migliore and colleagues
Dr. Migliore and his colleagues from the University of Catania, Policlinico Hospital, Catania, Italy

Technical Aspects on HITHOC

Thoracics.org: Does previous pleurodesis make surgery more difficult?

Dr. Migliore: Yes, due to the development of adhesions between parietal pleura and  the chest wall, as well as between the parietal and the visceral pleura, which are really difficult to remove.  It requires delicate work using the fingers ( at the end of the operation you can have pain in fingers and fingertips!)

Thoracics.org: Does it lead to increased operating room time, or increased bleeding from adhesions?

Dr. Migliore:  While is certainly increases operating time but there is no evidence of increased bleeding but air leaks are more frequent. Intraoperatively, it is imperative to put attention to every single detail to avoid postoperative complications.

Thoracics.org: Do you find that patients with diaphragm involvement develop more post-operative complications or are more likely to develop disseminated disease ?

Dr. Migliore: That has not occurred in this group of patients but the number of patients is small, and therefore it is impossible to answer.

Other considerations

Thoracics.org: What has been the biggest obstacle in your research?

Dr. Migliore: Certainly living in a “rural” region with cultural dogmas and financial restriction for research are probably the most common obstacles to speedy clinical surgical research.

On Hope & Malignant Mesothelioma

[During a related study] “We operated two patients and one is alive after 3 years. She was 40 y.o. lady with a 15 year-old child. She had malignant pleural effusion with a peripheral lung tumor and was treated elsewhere with talc pleurodesis alone, and 6 months survival was given. We performed a parietal and visceral pleurectomy with HITHOC. She is alive (with recurrence) and her son is now 18 yo. This simple case give an explanation that an operation although “experimental, gives hope (we should not give false hope) and permits to these unfortunate patients to see light in the dark”.

Dr. Marcello Migliore, MD

Thoracic Surgeon

Section of Thoracic Surgery

Department of General Surgery & Medical Specialities

University of Catania, Policlinico Hospital

Catania, Italy

Editor’s note:  Some minor edits have been made for the sake of formatting.  Thank you to Dr. Migliore and his team.

Mesothelioma, Hope and HITHOC

Is there hope? Thoracics.org discusses hope and mesothelioma along with the most recently published work in the area of cytoreductive surgery and intrathoracic chemotherapy (HITHOC).

Is there hope?

In a recent article in Future Oncology, Dr. Maat and his colleagues explore the question of whether hope exists for patients with malignant pleural mesothelioma (MPM).   The authors acknowledge the difficulties for patients and providers alike in maintaining hope when the odds are against it.  Dr. Maat also discusses the differences between offering false hope and belief in the possibilities of emerging therapies.

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“Dismal” prognosis of malignant mesothelioma

This brings to the forefront one of the biggest failures in thoracic surgery and oncology; malignant mesothelioma.  While great strides have been made in the last fifty years in the treatment of many other cancers, malignant mesothelioma continues to carry a dismal prognosis with a lifespan measured in months.  Not only that, but even the great “wins” in this area, like pleural decortication, are often only viewed as such when measured against palliative treatment (Zahid, Sharif, Routledge & Scarci, 2011).

This is one of the reasons Thoracics. org has taken such an interest in emerging therapies and research in areas such as HITHOC, and will continue to do so.  Sometimes even the most promising data takes a dead-end, like in the case of Dr. Isik in Ganziantep, Turkey, where HITHOC and mesothelioma research have been forced to take a backseat to ISIS and the Syrian refugee crisis.  This along with financial limitations (unfunded research) have threatened a promising program.

Dr. A. Feridun Işık and his team perform cytoreductive surgery and the HITHOC (HIPEC) procedure
Dr. A. Feridun Işık and his team perform cytoreductive surgery and the HITHOC (HIPEC) procedure (in 2014)

In situations like Dr. Isik’s, it is easy for readers and other researchers themselves to lose hope.  If programs showing favorable results like Dr. Isik’s can not survive, how can we expect support for additional research in this area?  But just as Dr. Maat advocates for hope among patients, and providers, we here at Thoracics.org continue to advocate for a hopeful future in the area of HITHOC; not just for malignant pleural mesothelioma, but for a whole spectrum of cancers that remain frustratingly difficult to treat.

Migliore et al. 

As such, Thoracics.org would like to highlight some of the most recent HITHOC publications.  Two of these studies are from Dr. Migliore and his colleagues at Catania, Italy.  The first paper, describes their preliminary experiences with eight patients (6 patients with MPM and 2 patients with lung cancer).  The authors discuss inclusion criteria, methodology and surgical technique (uniportal VATS/ and mini-thoracotomes) including one hour of chemoperfusion with cisplatin at 42.5 degrees centigrade.  Interestingly, in this tiny subset of patients, the surgeons included one patient who underwent diaphragmatic resection, which is usually considered a contraindication to the procedure according to most researchers*.  When we review the post-operative survival of these patients in this and the subsequent publication, it is worth asking about the specific survival time of the patient with diaphragmatic resection, and whether disease recurred in this specific patient.

The authors also included 2 patients with adenocarcinoma of the lung with pleural metastases in their priliminary series.  One of these patients had previously undergone talc pleurodesis.

Consistent with other recently published reports, mortality for this limited study was 0% (or much lower than what was previously reported during the “first generation” of cytoreductive surgery with hyperthermic chemotherapy in the early 2000’s).  Additional post-operative complications included 2 cases of post-operative nausea/ vomiting and one patient with acute kidney injury (post-operative creatinine 2.0).

The second publication by Migliore et al., also in Future Oncology is an expanded discussion of the six malignant pleural mesothelioma patients with better survival outcomes as 4 patients survival extended past the time of publication (one death at 6 months post-operative, one death at 24 months).

Anesthesia and HITHOC 

While this article dates back to mid 2014, Kerscher et al. is one of the only authors to investigate and describe the unique challenges for anesthesiologists managing these patients during the intra-operative and post-operative period.  Kerschner and colleagues report on their experiences with 20 patients undergoing cytoreductive surgery and HITHOC at the University Medical Center in Regensberg, Germany from 2008 to 2013.  In addition to describing the intra-operative anesthetic and post-operative analgesic techniques used as their institution, Kerscher et. al also delve into the specific management strategies related to the use of HITHOC, such as the addition of ventilatory peep during the cycling of hyperthermic chemotherapy to increase the amount of lung surface area exposed to the chemotherapeutic agents (cisplatin in this study).

Recommended reading

Their discussion of the management of intra-operative challenges caused by the infusion of chemotherapy such as low cardiac output, hypotension, pulmonary edema and coagulopathies along with an in-depth look at hemodynamics, volume resuscitation, challenges in ventilation and normothermia make this paper recommended reading for any surgeons or institutions interested in piloting their own HITHOC program.  This article also serves as a reminder that while many small studies report minimal complications, there can and are serious and potentially fatal intra-operative complications in patients undergoing HITHOC.

Like Dr. Hung and Dr. Chen, this paper serves an important reminder that all advancements and discoveries in thoracic surgery require a cohesive, teamwork approach.

*Most surgeons who perform HITHOC / HIPEC exclude patients with diaphragmatic involvement because this is believed to make it impossible to prevent widespread dissemination of disease – since the diaphragm is the physical, tissue barrier that separates the chest cavity from the abdomen.

References

Maat, A., Cornelissen, R., Bogers, J. & Takkenberg, J. (2015). Is the patient with mesothelioma without hope?  Future Oncol., 2015, 11 (24s), 11-14.

Migliore M, Calvo D, Criscione A, Viola C, Privitera G, Spatola C, Parra HS, Palmucci S, Ciancio N, Caltabiano R, Di Maria G. (2015).  Cytoreductive surgery and hyperthermic intrapleural chemotherapy for malignant pleural diseases: preliminary experience.  Future Oncol. 2015;11(2 Suppl):47-52. doi: 10.2217/fon.14.256.

Migliore M, Calvo D, Criscione A, Palmucci S, Fuccio Sanzà G, Caltabiano R, Spatola C, Privitera G, Aiello MM, Parra HS, Ciancio N, Di Maria G. (2015).   Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.  Future Oncol. 2015 Nov;11(24 Suppl):19-22. doi: 10.2217/fon.15.286.

Kerscher C, Ried M, Hofmann HS, Graf BM, Zausig YA. (2014).  Anaesthetic management of cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy perfusion.  J Cardiothorac Surg. 2014 Jul 25;9:125. doi: 10.1186/1749-8090-9-125.  An excellent overview of intra-operative management considerations for patients undergoing HITHOC procedures.  Recommended reading.