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.
“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.
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).
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.
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.