A closer look at HITHOC in Germany

A look of HITHOC in two programs in Germany, Freiburg and Regensburg

While there are a reported 17 centers in Germany performing the HITHOC procedure, this, dear readers, is the tale of two cities.

Over the years, finding information and making contact with surgeons performing the HITHOC procedure has been a long, expensive and time-consuming affair.  Emails, interview requests and research questions frequently go unanswered.  Expensive trips abroad for in-person interviews  sometimes end up with all-too-brief meetings with disappointing results.  But illuminating, and informative interviews and in-depth discussions about HITHOC are worth the inconvenience.

After the publication of a brief English language abstract for a larger article in German that hinted at research outcomes for multiple facilities, thoracics.org reached out several times to the authors (Ried et al, 2018) for further comment.

Back in 2011, Dr. Ried and his colleague, Dr. Hofmann at the University Medical Center in Regensburg, Germany, briefly discussed their HITHOC program, which was started in 2008.

Now, thoracics.org is in Germany to talk with Dr. Hofmann as well as another thoracic surgeon at a different facility in southwestern Germany.

sign
Heading south to Freiburg im Breisgau

Our journey starts just a few hours south of Frankfurt, in the picturesque city of Freiburg im Breisgau, in the Black Forest region of Germany best known for Cuckoo clocks, the Brothers Grimm fairy tales chocolate cake, and thermal spas.  Freiburg is the largest city in this region.  It’s a charming locale with a history that extends back to medieval times despite Allied bombing in a more recent century.

church
Freiburg is known for it’s massive cathedral, Munster Unserer Lieben Frau (Cathedral of our Lady).  Construction began in 1200 and was completed over 315 years later.

 

Frieburg is also home to a University Hospital and the Robert Koch clinic of thoracic surgery.  Dr. Bernward Passlick is the Director and head surgeon of this department.

clinic sign

Dr. Passlick is the reason thoracics.org has come to this charming but sleepy college town.  After several months of written correspondence, thoracics.org arrived in Freiburg to here more about the HITHOC program from Dr. Passlick himself.

However, from the first initial comments from the department secretary who lamented that the length of HITHOC cases was “a waste of operating room time” [because multiple other cases could be done in the time it takes to perform one HITHOC case], to the actual meeting with Dr. Passlick, nothing proceeded as expected.  Dr. Passlick was uninterested, and unwilling to discuss HITHOC.  He reported that he did approximately 15 cases a year, retains no outcomes data and has no interest in publishing any results from these cases.  However, despite the apparent lack of any documentation or statistics on HITHOC cases performed at the facility in Freiburg, he states that the ‘average’ survival is 2 to 3 years with some long-term survivors at six years or more, post-procedure.  [When asked when he had no interest in publishing data showing six year survival, Dr. Passlick had no answer.  We sat in silence for a few minutes, until I thanked him for his time and left.]

He briefly mentioned that his real interest lay in the area of treating multiple pulmonary metastasis using laser assisted resection via open thoracotomy.  The laser resection technique allows for greater lung sparing in patients with multiple (and presumably, bilateral) pulmonary metastases from other primary cancers such as advanced colon, renal or breast cancer.  He uses this technique for patients with five or more pulmonary metastasis, and reports he has operated on patients with as many as 20 to 25 metastatic pulmonary lesions.  He didn’t have any statistics on this procedure to share, but did offer that he has a paper scheduled for publication soon.  So, a bit disheartened, and thus unenlightened, it was time to leave Freiburg.

canals
the canals of Freiburg in the historic district

Leaving the Black Forest, we head east – into Bavaria with miles of rolling hills dotted with windmills, vineyards and solar panels, past Munich and then north into the area where the Danube, the Naab and the Regen rivers meet. This is Regensburg, a city that was founded by the Celts.  The Romans later built a fort here in 90 CE.  The remains of a later Roman fort are readily seen in the historic city center.

roman ruins
Part of old Roman fortress in the historic quarter of Regensburg

But as charming as the city of Regensburg is, we aren’t here for sightseeing.   Our next stop is another HITHOC program.  It’s not the biggest in Germany, not by far, but it is a very well established program that is grounded in evidence-based practice, protocols and on-going scientific inquiry and research.

We are here to interview Dr. Hans – Stefan Hofmann, the head of the thoracic surgery department at both the University hospital and the large, private Catholic hospital in town.  Dr. Hofmann along with his colleague, Dr. Michael Reid.

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Re-assuredly, the interviews were more familiar territory.  Dr. Hofmann was very friendly, and forth-coming.  Dr. Hofmann reports that their HITHOC volumes are fairly small, and attributes this to plateauing rates of pleural mesothelioma.  (The majority of the HITHOC cases were initially performed for pleural mesothelioma, but there have been an increasing number of cases treating advanced thymomas (stage IV) with HITHOC as well as limited cases of pleural carcinosis.

In some of these thymoma cases, the patient undergoes a staged procedure, with mediastinal exploration performed as the first step.  In some cases, the Regensburg facility receives patients after they have undergo mediastinal lymph node dissection at another facility.

Hofmann
Dr. Hans – Stephan Hofmann, Director of Thoracic Surgery

His program has been performing HITHOC for over ten years, using a combination of cisplatin and doxirubin with a cycle time of 60 minutes.  He reports a low rate of complications and points to the multiple publications by his colleague, Dr. Reid for outcome data.  Dr. Reid has another couple of articles in press including another paper, that explains their renal protection protocol, [in addition to Reid’s earlier work in 2013, listed below].

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Dr. Michael Reid (left) with Dr. Hans Stephen Hofmann

Of course, the visit wouldn’t be complete without a trip to the operating room.  While it wasn’t a HITHOC case, Dr. Hofmann was performing a robotic -assisted thoracoscopic surgery on a patient requiring lung resection for adenocarcinoma.  As the patient was already medicated when I entered the operating room – there are no operating room photos.   The case proceeded quickly, efficiently with no intra-operative complications and minimal EBL.

HofmannOR
Outside the operating room

As some of our long time readers know, thoracics.org no longer just reports on news and events in thoracic surgery.  After multiple requests from our readers, we now facilitate specialty treatment too.  

We won’t talk about that a lot here – it’s not the right forum, but for readers who would like more information about Dr. Hofmann, or are interested in surgery with Dr. Hofmann (or Dr. Gonzalez Rivas, Dr. Sihoe or any of the other modern Masters of thoracic surgery), we  are happy to assist you.  Contact me at kristin@americanphysiciansnetwork.org

thoracics OR Regensburg
In the operating room, with the robot behind me (case is over).

Selected citations

Both surgeons are widely published on multiple thoracic surgery topics.  This is a limited selection of citations related to HITHOC.

Ried M, Hofmann HS, Dienemann H, Eichhorn M.  (2018).  [Implementation of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Germany].  Zentralbl Chir. 2018 Jun;143(3):301-306. doi: 10.1055/a-0573-2419. Epub 2018 Mar 12. German.  PMID: 29529693   It was an article similar to this that started thoracics.org journey to Germany.

Ried M, Marx A, Götz A, Hamer O, Schalke B, Hofmann HS.  (2016).  State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma.  Eur J Cardiothorac Surg. 2016 Jun;49(6):1545-52. doi: 10.1093/ejcts/ezv426. Epub 2015 Dec 15. Review.  PMID:26670806

Hofmann HS, Wiebe K. (2016). [Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion].  Chirurg. 2010 Jun;81(6):557-62. doi: 10.1007/s00104-010-1926-2. Review. German.  PMID: 20454769   

 

Ried M, Lehle K, Neu R, Diez C, Bednarski P, Sziklavari Z, Hofmann HS. (2015). Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure.  Eur J Cardiothorac Surg. 2015 Mar;47(3):563-6. doi: 10.1093/ejcts/ezu217. Epub 2014 May 28.  PMID:  24872472

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.

Ried M, Potzger T, Braune N, Neu R, Zausig Y, Schalke B, Diez C, Hofmann HS. (2013).  Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience.  Eur J Cardiothorac 2013 Apr;43(4):801-7. doi: 10.1093/ejcts/ezs418. Epub 2012 Aug 10.  Early article on their HITHOC results with 8 patients.

Ried M, Hofmann HS. (2013).  [Intraoperative chemotherapy after radical pleurectomy or extrapleural pneumonectomy].  Chirurg. 2013 Jun;84(6):492-6. doi: 10.1007/s00104-012-2433-4. Review. German.  PMID:  23595855

Ried M, Hofmann HS. (2013).  The treatment of pleural carcinosis with malignant pleural effusion.  Dtsch Arztebl Int. 2013 May;110(18):313-8. doi: 10.3238/arztebl.2013.0313. Review.  PMID:  23720697   Link to article in english discussing limited utility of HITHOC for pleural carcinosis.

 

Ried M, Neu R, Schalke B, Sziklavari Z, Hofmann HS. (2013).  [Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread]. Zentralbl Chir. 2013 Oct;138 Suppl 1:S52-7. doi: 10.1055/s-0033-1350869. Epub 2013 Oct 22. German.  PMID: 24150857

Ried M, Potzger T, Braune N, Diez C, Neu R, Sziklavari Z, Schalke B, Hofmann HS. (2013).  Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.  J Surg Oncol. 2013 Jun;107(7):735-40. doi: 10.1002/jso.23321. Epub 2013 Feb 5.  PMID:  23386426.  Discussed the effects of cisplatin on tissue.

Ried M, Speth U, Potzger T, Neu R, Diez C, Klinkhammer-Schalke M, Hofmann HS. (2013).  [Regional treatment of malignant pleural mesothelioma: results from the tumor centre Regensburg].  Chirurg. 2013 Nov;84(11):987-93. doi: 10.1007/s00104-013-2518-8. German.  PMID:  23743993

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.

Germany

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.

Italy

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.

China

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?

 

References

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 

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.

Dr. Ahmet F. Işık talks about pleural mesothelioma, HITHOC, and thoracic surgery in Gaziantep, Turkey

updates on the on-going HITHOC project, war surgery, foreign body obstructions and bronchoscopy for infants

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Gaziantep, Southeastern Anatolia 

antep

It’s been over a year since I first read Dr. Isik’s work on treating pleural mesothelioma.  Since that time, Dr. Işik has continued his research into HITHOC and has now enrolled over 79 patients into the hyperthermic treatment group including one of the patients I met during my visit.  (There are 29 surviving patients in the study, 13 in the mesothelioma group, the remainder are secondary pleural cancers.).

(If you are a patient seeking treatment, or would like more information about Dr. Isik (or Dr. Gonzalez Rivas, Dr. Sihoe or any of the other modern Masters of thoracic surgery), we  are happy to assist you.  Contact me at kristin@americanphysiciansnetwork.org

First impressions are deceiving

I don’t know what I expected Gaziantep to look like as one of the world’s oldest cities, but from the moment the airplane begins its descent into a beige dust cloud, to the desolate brush and dirt of the airport outside the city, it isn’t what I expected.  Much of the antiquity of the biblical city of Antiochia has been replaced by a bustling modern city.  Historic ruins and ancient Roman roads marking this as part of the original Silk Road are conspicuous, only by their scarcity.

modern Gaziatep is featureless at first glance
modern Gaziantep is featureless at first glance

There are a handful of museums and monuments to the area’s rich history, but like the new name of Gaziantep (replacing Antep after the first world war), Turkey’s sixth largest city is modern; a collection of traffic and squat square buildings of post-modern architecture.

Kale
Kale

The city is also a mosaic of people.  There are groups of foreign journalists in the lobby of our hotel, and convoys of United Nations vehicles cruising the streets.  Crowds of Syrian children play in the park, calling out in Arabic to their parents resting on the benches nearby.  There is a smattering of Americans and English speakers interspersed, many are college students and other foreign aid workers on humanitarian missions to help alleviate the strain caused by large numbers of people displaced by the Syrian civil war.

Gaziantep is famed for their copper work
Gaziantep is famed for their copper work

But like a mosaic, there is always more to see, the closer you look.  For me, as I look closer, I just want to see more.  I feel the same about Dr. Elbeyli’s thoracic surgery department.

The closer you look, the more you see. photo courtesy of wiki-commons
The closer you look, the more you see.
photo courtesy of wiki-commons

The border (and the largest Syrian city of Aleppo) lies just to the south – and the impact of the Islāmic militants is felt throughout the region.  No where is this more evident than at the local university hospital, where I meet Dr. Ahmet Işık and the Chief of Thoracic Surgery, Dr. Levent Elbeyli.

with Dr. Elbeyli (left) and Dr. Isik
with Dr. Elbeyli (left) and Dr. Isik

Dr. Ahmet Feridun Işık

I like Dr. Işık immediately.  He is friendly and appears genuinely interested by my visit.  He’s from Giresun in the Black Sea region of northern  Anatolia of Turkey.  He attended medical school at Ankara University and completed his thoracic surgery training in Ankara before going to Adiyaman State Hospital in the bordering Turkish province of Adiyaman in southeastern Turkey.

He was an associate professor of thoracic surgery at Yuzuncu Yil University in the far eastern province of Van, Turkey before coming to Gaziantep in 2005.  He became a full professor at the University of Gaziantep in 2013.  In additional to authoring and contributing to his own publications, he also served as a reviewer for the Edorium series of open access journals.

It helps that his English is miles better than my non-existent Turkish.  (Reading about the Turkish language in phrase books is one thing, pronouncing words correctly is another.)

He doesn’t seem to mind my questions tumbling out one after another.  I’d like to be the cool, sophisticated visitor, but I’ve been waiting so long to ask some of these questions – and frankly, I am just excited to be there.

Dead-ends in medicine

There are a lot of “dead ends” in medicine – treatments that at first appear promising, but then end up being either impractical or ineffective.  In fact, for the first ten years of HIPEC, most surgeons dismissed it as a ‘dead-end’ treatment; the surgery was too radical and mortality too high.  But researchers kept trying experimental protocols; tweaking medications (less toxic) and procedures – and finding the right patients (not too frail prior to surgery) – and the literature shifted; from a largely useless ‘last ditch’ salvage procedure to a large, but potentially life-saving treatment. HITHOC is HIPEC in another color…

So I fire away –

Since our last post about Dr. Işık – he has performed several more cases of HITHOC on patients with pleural mesothelioma, pleural based cancers and advanced lung cancers.  He now has 79 patients in the HITHOC treatment group.  He has been receiving patients from all over Turkey, including Istanbul to be evaluated for eligibility for this procedure.  While the majority of patients are referred by their oncologists, others come to Gaziantep after reading about Dr. Işık on the internet.

None of the original patients (from 2009) are still alive, but their survival still exceeded all expectations, with 13 patients (of 14 HITHOC patients) living 24 to 36 months after the procedure.  (I don’t mean to be vague – but I was asking some of these questions in the operating room and I forgot to stuff my little notebook in my scrub pocket.)

While much of the literature surrounding the procedure cites renal failure as one of the major complications of the procedure, Dr. Işık has had one case of renal failure requiring dialysis.  Any other instances of elevated creatinine were mild and transient.  He doesn’t use any chemical renal prophylaxis but he does use fluid rehydration to limit nephrotoxicity.

He reports that while many surgeons consider sarcomas to be a contraindication to this procedure, he has had good outcomes with these patients.

He does state that diaphragmatic involvement in mesothelioma is an absolute contraindication because while the diaphragm can be resected / patched etc, it is almost impossible to guarantee or absolutely prevent the seeding of microscopic cancer cells from the diaphragm to the abdominal cavity – which increases the risk of disseminated disease.

He still uses Cisplatin – since that is what the original HITHOC researchers were using, but he uses a slightly higher dose of 300mg.  He’d like to do some prospective studies utilizing HITHOC (these have all been retrospective in nature – comparing today’s patients with past patients that received PDD and pleurodesis for similar conditions).  Prospective studies would allow him to better match his patients and to compare treatments head to head.  It would also allow him to compare different techniques or chemotherapeutic agents.

Unfortunately, as he explained, many of these types of studies of ineligible for government funding in Turkey because the government doesn’t want to pay for experimental / unproven treatments for patients even if there are few or no alternatives for treatment.  He is hoping to appeal this regulation so that he can continue his research since there is such a high rate of mesothelioma, that disproportionately affects rural Turkish patients.

 The University of Gaziantep Hospital

The University of Gaziantep Hospital

The University Hospital is one of several hospitals in Gaziantep.  The academic institution has over 900 beds and 20 operating rooms spread out over three floors.  There is a large 24 bed surgical ICU which includes 4 dedicated thoracic surgery beds.

Thoracic surgery may not be the advertised superstar of the hospital but it is the backbone of patient care.  There are three full-time professors of surgery; Dr. Ahmet Isik, Dr. Levent Elbeyli and Dr. Bulent Tunçözgür, along with an associate professor, Dr. Maruf Sanli, several thoracic surgery fellows and research assistants.  Together the thoracic surgery team performs over 1000 cases a year.

Dr. Levent Elbeyli is the driving force for thoracic surgery.  A Gaziantep native, he founded the department in 1992, and has seen it grow from a few scattered beds to a full-fledged program with a full-time clinic, 2 dedicated operating rooms, 4 ICU beds and 15 to 20 cases a week.

Dr. Levent Elbeyli (in loupes) in the operating room
Dr. Levent Elbeyli (in loupes) in the operating room

For the thoracic nurse, the department of Thoracic Surgery is a dream come true; tracheal cases, surgical resections, esophagectomies, thoracic trauma – all of the bread and butter that makes our hearts go pitter-pat.  But then there is also plenty of pediatric cases, pectus repair, foreign body removal (oro-esophageal) and on-going surgical research.  They do a large amount of pediatric and infant bronchoscopies (for foreign body obstructions, tracheal malformations etc).

There is the slightly exotic hydatid cysts and the more mundane (but my personal favorite) empyema thoracis to be treated.  Cancers to be staged, and chest wall resections to undertake.  I feel almost overwhelmed in my own petite version of a candy store; everywhere I turn I see opportunities to learn, case reports to write and new things to see.

Dr. Levent Elbeyli operates as Dr. Isik observes.
Dr. Levent Elbeyli operates as Dr. Isik observes.

My non-medical readers might be slightly repulsed by my glee – but it is this intellectual interest that keeps me captivated, engaged and enamored with thoracic surgery and caring for thoracic surgery patients.   And then there is the HITHOC program.  With a large volume of mesothelioma and pleural based cancers due to endemic environmental asbestos in rural regions of Turkey, there is an opportunity to bring hope and alleviate suffering on a larger level.  (Dr. Isik sees more cases here in his clinic in one year than I have seen in my entire career).

What’s not to love about that?

Article updates:

Since our original visit to Dr. Isik, he has continued his work on HITHOC for malignant pleural mesothelioma and other cancers.  You can read his latest paper, “Can hyperthermic intrathoracic perfusion chemotherapy added to lung sparing surgery be the solution for malignant pleural mesothelioma?

In this study, Dr. Isik and hs team looked at 73 patients with malignant pleural mesothelioma (MPM) who were in three different treatment groups.  Group 1 received surgery only (extrapleural pneumonectomy).  Group 2 received palliative treatment only.  Group 3 received lung sparing surgery with hyperthermic chemotherapy (HITHOC).  Lung sparing surgery included pleural decortication.

While the treatment groups are small, the results show a clear survival benefit to the patients receiving HITHOC.   Surprisingly, the palliative group lived longer than the surgery alone group.

Survival based on treatment modality:

Surgery only:  5 months average surgery.  15% survival at 2 years

Palliative treatment only: 6 months average survival   17.6% at 2 years

HITHOC group:  27 months average survival    56.5% at 2 years

Selected Bibliography for Dr. Işık  

Işık AF, Sanlı M, Yılmaz M, Meteroğlu F, Dikensoy O, Sevinç A, Camcı C, Tunçözgür B, Elbeyli L (2013). Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies. Respir Med. 2013 May;107(5):762-7. doi: 10.1016/j.rmed.2013.01.010. Epub 2013 Feb 23. The article that brought me to Turkey, and part of our series of articles on the evolving research behind HITHOC.

Isik AF, Tuncozgur B, Elbeyli L, Akar E. (2007).  Congenital chest wall deformities: a modified surgical technique.  Acta Chir Belg. 2007 Jun;107(3):313-6.

Isik AF, Ozturk G, Ugras S, Karaayvaz M. (2005).  Enzymatic dissection for palliative treatment of esophageal carcinoma: an experimental study.  Interact Cardiovasc Thorac Surg. 2005 Apr;4(2):140-2. Epub 2005 Feb 16.

Er M, Işik AF, Kurnaz M, Cobanoğlu U, Sağay S, Yalçinkaya I. (2003).  Clinical results of four hundred and twenty-four cases with chest trauma. Ulus Travma Acil Cerrahi Derg. 2003 Oct;9(4):267-74. Turkish.

Sanli M, Arslan E, Isik AF, Tuncozgur B, Elbeyli L. (2013). Carinal sleeve pneumonectomy for lung cancer. Acta Chir Belg. 2013 Jul-Aug;113(4):258-62.

Maruf Şanlı, MD, Ahmet Feridun Isik, MD, Sabri Zincirkeser, MD, Osman Elbek, MD, Ahmet Mete, MD, Bulent Tuncozgur, MD and Levent Elbeyli, MD (2008). Reliability of positron emission tomography–computed tomography in identification of mediastinal lymph node status in patients with non–small cell lung cancer. The Journal of Thoracic and Cardiovascular Surgery, Volume 138, Issue 5, Pages 1200–1205, November 2009.

Sanlı M, Isik AF, Tuncozgur B, Elbeyli L. (2009).  A new method in thoracoscopic inferior mediastinal lymph node biopsy: a case report.  J Med Case Rep. 2009 Nov 3;3:96. doi: 10.1186/1752-1947-3-96.

Sanli M, Isik AF, Zincirkeser S, Elbek O, Mete A, Tuncozgur B, Elbeyli L. (2009).  The reliability of mediastinoscopic frozen sections in deciding on oncological surgery in bronchogenic carcinoma. J Thorac Cardiovasc Surg. 2009 Nov;138(5):1200-5. doi: 10.1016/j.jtcvs.2009.03.035. Epub 2009 Jun 18.

Sanli M, Işik AF, Tunçözgür B, Arslan E, Elbeyli L. (2009).  Resection via median sternotomy in patients with lung cancer invading the main pulmonary artery.  Acta Chir Belg. 2009 Jul-Aug;109(4):484-8.

Sanli M, Isik AF, Tuncozgur B, Elbeyli L.  (2010).  Successful repair in a child with traumatic complex bronchial rupture.  Pediatr Int. 2010 Feb;52(1):e26-8. doi: 10.1111/j.1442-200X.2009.03000.x

Sanli M, Işik AF, Tunçözgür B, Meteroğlu F, Elbeyli L. (2009).  Diagnosis that should be remembered during evaluation of trauma patients: diaphragmatic rupture].  Ulus Travma Acil Cerrahi Derg. 2009 Jan;15(1):71-6. Turkish.

Dr. David Sugarbaker comes to Texas, and too much of a good thing!

Big reputations and legendary surgeons require big opportunities – and as everyone knows; every thing is bigger in Texas.

Dr. David Sugarbaker, one of the legendary American thoracic surgeons has left his position at Brigham and Women’s Hospital in Boston to join Baylor St. Luke’s Medical Center in Houston, Texas.

Dr. Sugarbaker comes to Texas to lead the new Lung Institute at the College of Medicine (Baylor University).

I’m keeping my fingers crossed that this means I have another chance to cross paths with Dr. Sugarbaker when I return to Texas in May.  I would love to talk to him about mesothelioma, HITHOC and the new Lung Institute.

In other news – It’s been too much of a good thing for our Thoracic Surgery app.  So many people have downloaded and used the application – that the hosting service will no longer support and host the application for free.  (Unfortunately, due to financial constraints – I am unable to pay for continued support and hosting services).  So thanks to everyone who made this application a success – and my apologies that I am no longer able to maintain it.

St. George’s Hospital, NHS and the state of thoracic surgery

A visit to St. George’s Hospital in South London to talk about the state of thoracic surgery in Great Britain.

St. George’s Hospital – South London, UK

St. George’s Hospital is one of the largest teaching hospitals in the United Kingdom. In fact, with over 1,000 beds, St. George’s is the largest hospital in London, and one of the largest hospitals in Great Britain. Historically, St. George’s Hospital was the home of several prominent, and important figures in medicine and surgery, including Henry Gray (author of the classic Gray’s Anatomy text, and early anatomist), noted surgeon John Hunter (often called the ‘father of modern surgery’). Edward Jenner, inventor of the smallpox vaccine, also practiced at St. Georges.

on the grounds of St. George’s Hospital

The hospital campus itself has an interesting story, after being founded in 1733.  Originally located in central London, after several moves and upgrades, it was finally removed to its current location in the working class, ethnically diverse neighborhood of Tooting in South London in 1980. (Hospital services, including the University of London medical school were moved to the Tooting site in multiple stages, starting in 1954.)

Tooting, UK

All of this makes for a fascinating backdrop for my visit to talk to British surgeons about thoracic surgery in the United Kingdom.  The hospital has a dedicated cardiothoracic surgery division, located within the Atkinson Morley Wing (which also houses neurosurgery and cardiology facilities.)

The cardiothoracic surgery division and the subspecialty area of thoracic surgery are well-defined here, with multiple ancillary services such as pulmonary rehabilitation programs and is collectively known as the Chest center. The Chest Center is made up of a multi-disciplinary team which includes two thoracic surgeons, two cardiothoracic surgeons, a pulmonary interventionalist (a pulmonologist specializing in interventions such as bronchoscopy), and a nurse practitioner (known as nurse specialists in the UK). It’s a busy service line, performing over 1100 surgeries per year.

And so, I found myself spending a gray, rainy afternoon discussing the state of thoracic surgery in the United Kingdom with two very fine surgeons from St. George’s Hospital.   Like many of the surgeons I have interviewed, they were modest, humble even about the important work that they do for the citizens of Surrey and West Essex counties.  As a stranger to socialized medicine and the National Health Service, we started a conversation discussing some of the international headlines discussing thoracic surgery in the UK.

Contrary to recent media reports suggesting a decay in services for British citizens, the surgeons I spoke to (Hunt and Tan[1]) state that thoracic surgery is undergoing a renaissance period over the last few years: the number of dedicated specialty trained[2] thoracic surgeons have actually increased dramatically, and has almost doubled, from around forty surgeons to more than 70.   The recent 2011 national audit showed an increase in both percent and total cancer operations and a dramatic decrease in surgical mortality.

This new generation of thoracic surgeons heralds a new, hopeful era for thoracic surgery in Great Britain.  These new (and for the most part, younger) surgeons, in turn, embrace newer procedures and technologies for treatment of thoracic diseases.   As thoracic surgeons, (versus traditional cardiothoracic surgeons) these doctors have more in-depth knowledge and interest in state-of-the-art therapies for lung cancer and other thoracic conditions.  This is particularly important, as here in England, similar to many of the locations I have visited, newer technologies have advanced much quicker than the slower moving bureaucracies such as medical billing and reimbursement[3].  This means that there is often little financial incentive for surgeons to learn, adopt and embrace innovative techniques or even established advancements such as video-assisted thoracoscopy (VATS)[4]. The hospitals and the divisions they work for receive greater reimbursement for the larger, more traditional ‘open’ surgeries even if the patients are best served by smaller, minimally invasive procedures.

The thoracic surgeons at St. George’s have managed to circumvent much of this mentality by using existing data from their own program to show the benefits of minimally invasive surgery. Much of this data has been collected as part of the national database called the ‘Blue Book.’ This national audit of surgical practices and outcomes is similar to the Society of Thoracic Surgeons (STS) database, and is entirely voluntary [5].  However, unlike the STS General Thoracic database which is currently poorly attended by American surgeons – the Blue Book is well-populated by British surgeons, with 100% participation [6].

The most recent data from St. George’s suggests that all of these developments are making a difference.  The two thoracic surgeons, Ian Hunt, and Carol Tan are both part of that new generation of innovators, and researchers.  They report that they are doing more and more VATS procedures (as part of the 8 – 12 cases they are doing every week).  They are doing more and more procedures on older patients – and sicker patients with more advanced cancers – with positive outcomes.  The average VATS patient length of stay is 3 days, and even patients undergoing large open traditional cases are going home in five or six days.  They have replaced epidurals with PCAs and one time spinal injections to increase patient mobility, and continue to investigate ways to reduce pneumonias and other post-operative complications.

Recent changes within the national health service have sometimes made this more difficult.  Patient privacy and new public health policies make investigational trials more cumbersome and time-consuming, but it doesn’t dampen their enthusiasm.

I can’t talk about St. Georges and Thoracic Surgery without further mentioning the surgeons that help make St. George’s Hospital the top #2 or #3 institution in the UK for patient care.  As I’ve mentioned, Mr. (Dr.) Ian Hunt, FRCS, MD is a humble sort of gentleman.  He is also an enthusiastic, friendly and fascinating interview.

In just 2010 and 2011 alone, he was involved in at least six research papers published on two continents (see below).  These papers span the spectrum of thoracic surgery topics – from metastasectomy in colon cancer to cryoablation for chest wall pain, to thoracic trauma and the use of video mediastinoscopy.

I haven’t seen him operate, but he has the qualities that seem universal and essential in the make-up of outstanding modern surgeons [7].  One of these qualities is relentless pursuit of academic and surgical knowledge.  This pursuit has led Mr. Hunt across three continents and several countries, as he travelled to Alberta, (Canada), New Zealand and the United States for education and training that was not available in the UK.  He has a keen interest in pursuing research and answers for the conditions that plague his patients the most; surgical resections for advanced cancers, mediastinal surgery and chest wall reconstructions, thoracic trauma, mesothelioma and airway disease.  He is also interested in research and predictive tools such as the ThoracoScore (used to predict post-operative mortality – similar to the Surgical Apgar [8].)

His colleague, fellow surgeon, Carol Tan joins us during the interview.  She came to St. George’s Hospital several months after Ian Hunt, and together they have been instrumental in creating a ‘atmosphere of change’ at St. Georges.  We spend a few minutes talking about epidemiologic patterns of lung diseases.  In comparison to other geographic areas, urban London sees more seasonal empyema patterns related to parapneumonic infections, but less chronic diseases such as tuberculosis and opportunistic fungal infections.  We discuss how the use of long-term antibiotic therapy regimens has complicated the identification and diagnosis of causative organisms.  We also discuss her interests in the treatment of pleural disease and St. George’s surgical programs for myasthenia gravis (in conjunction with spine surgeons) and the benefits of unconventional transcervical approaches instead of median sternotomy.  Both Mr. Hunt and Ms. Tan also talk about the increasing use of ‘co-surgeons’ in the operating room, the advantages of this practice and how this is changing surgery.

Together, we discuss the Davies article and how this skewed view of the roles of pulmonary medicine and thoracic surgery mirrors many of the conflicts in cardiology and cardiac surgery [9].  We also discuss how referral patterns and timing of referrals also affects surgical outcomes and the co-dependency among specialists.

Before the end of the interview, we also talk about another faucet of thoracic surgery (that is near and dear to my heart): the use  and role of nurse practitioners in thoracic surgery.  Unfortunately, Caroline, the nurse specialist in thoracic surgery at St. George’s is unable to join us today.  But maybe another day.


[1] “Please make the article about thoracic surgery, and what we do, not about us,” Mr. Hunt requests. In response, I have done so, but will give brief mention of both Mr. (Dr.) Ian Hunt and Ms. (Dr.) Carol Tan at the conclusion of this article, to give readers a better idea of the speakers qualifications and background.

[2] This refers to surgeons specifically focusing on thoracic surgery, as opposed to traditional cardiothoracic surgeons who are dual specialized, or general surgeons (who have omitted specialty training) but may perform thoracic procedures.

[3] This seems to be a fairly common situation in medicine, around the world.  Influence of conversion on cost of video-assisted thoracoscopic lobectomy, Eur J Cardiothorac Surg. 2010 Jan;37(1):249-50; author reply 250-1. Epub  2009 Dec 5.

[4] Learning these techniques often comes at considerable expense, and inconvenience for many of these surgeons – who may have to travel to North America, Hong Kong or other large centers specializing in minimally invasive surgery for fellowships or periods of extended training.

[5] While entirely voluntary, there is a stigma attached to surgeons who do not participate under the assumption as to the reasons why they do not want their hospital, thoracic surgery program and individual surgeon data disclosed to the public.

[6] The British Blue Book is not specific to thoracic surgery only.  Several other specialties such as orthopaedics contribute to this database.  However, the cardiothoracic specialty is overseen by the Society of Cardiothoracic Surgery.

[7].  The qualities of outstanding modern and historical surgeons differ greatly.  One of the most important qualities in surgeons past was fearlessness.  These surgeons often endured failure after failure (patient deaths) before developing effective surgical techniques.  As you can imagine, this quality of fearlessness would now be seen as recklessness – and would not be a desirable trait in modern surgeons for many reasons.

[8] As we discussed previously, Davies work ignores much of the existing research that demonstrates conflicting results to their opinions – including their own research which failed to confirm their propositions.

[9]  The Surgical Apgar scoring system by Gwande predicts post-operative mortality and complications by measuring 4 intra-operative factors.

Additional Resources:

History of the University of London Medical School

The Society for Cardiothoracic Surgery

The Blue Book reports


Selected bibliography of Mr. Ian Hunt
* denotes lead author
(2011).  Cadaveric thoracic trauma management courses for emergency physicians may contribute to improved outcomes.  Eur J. Emerg Medicine 2011 Nov 22.
(2011).  A method of assessing reasons for conversion during video-assisted thoracoscopic lobectomy .  Interact Cardiovasc Thorac Surg 2011 Jun 12 (6).
*(2010).  Managing a solitary fibrous tumour of the diaphragm from above and below.  ANZ J Surg 2010 May, 80 (5) 370-1.
*(2010).  A late complication of traumatic flail segment with colonic herniation.  Emerg Med J. 2010 Mar, 27 (3) 193.
*(2010).  Video-assisted intercostal nerve cryoablation in managing intractable chest wall pain.  J Thorac Cardiovasc Surg. 2010 Mar;139(3):774-5.
*(2009).  Minimally invasive excision of a mediastinal cystic lymphangiomaCan J Surg. 2009 Oct;52(5):E201-2.  case report.
(2009).  Novel fixation technique for the surgical repair of lung hernias.  Ann Thorac Surg. 2009 Sep;88(3):1034-5.
(2009).  Massive pulmonary arteriovenous malformation presenting with tamponading haemothoraxBMJ Case Rep. 2009;2009:bcr2006071852. Epub  2009 Feb 18.  case report.

Ms. Carole Tan, MD, FRCS(C) is a board-certified thoracic surgeon.  She joined the Chest Center at St. George’s Hospital in 2010.  She is currently the principal investigator for PulMiCC (pulmonary metastasectomy for colorectal carcinoma.)
Ms. Tan’s clinical interests include the treatment of pleural disease, specifically malignant mesothelioma, which we have talked about on previous occasions at Cirugia de Torax.  In fact, she has been widely published in this area (see bibliography below.)  Prior to coming to St. George’s Hospital, Ms. Tan was the surgical coordinator for the multicenter MARS trial (on the surgical treatment of malignant mesothelioma).
Ms. Tan has also been involved in several studies on the use of sealants intra-operatively for the treatment of air leaks, and chest tube suction.
Bibliography for Ms. Carole Tan
In press:
Zakkar M, Tan C, Hunt I. Is video mediastinoscopy a safer and more effective procedure than conventional mediastinoscopy? Interact Cardiovasc Thorac Surgery.
Tan C, Treasure T, Utley M. Reply to D’Andrilli and Rendina. Eur J Cardiothorac Surgery.
PUBLICATIONS
Bliss JM, Coombes G, Darlison L, Edwards J, Entwistle J, Kilburn LS, Landau D, Lang-Lazdunski L, O’Brien M, O’Byrne K, Peto J, Senan S, Snee M, Spicer J, Tan C, Thomas G, Treasure T, Waller D. The MARS feasibility trial: conclusions not supported by data – Authors’ reply. Lancet Oncol 2011;12(12):1094-5.
Treasure T, Lang-Lazdunski L, Waller D, Bliss JM, Tan C, Entwisle J, Snee M, O’Brien M, Thomas G, Senan S, O’Byrne K, Kilburn LS, Spicer J, Landau D, Edwards J, Coombes g, Darlison L, Peto J; MARS trialists. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 2011;12(8):763-73.
Tan C, Utley M, Paschalides C, Pilling J, Robb JD, Harrison-Phipps KM, Lang-Lazdunski L, Treasure T. A prospective randomised controlled study to assess the effectiveness of CoSeal to seal air leaks in lung surgery. Eur J Cardiothorac Surg 2011;40(2):304-8.
Teh E, Fiorentino F, Tan C, Treasure T. A systematic review of lung-sparing extirpative surgery for pleural mesothelioma. J R Soc Med 2011;104(2):69-80.
Tan C, Barrington S, Rankin S, Landau D, Pilling J, Spicer J, Cane P, Lang-Lazdunski L. Role of integrated 18-FDG-PET-CT in patients surveillance after multimodality therapy of malignant pleural mesothelioma. J Thorac Oncol 2010;5(3):385-8.  Treasure T, Waller D,
Tan C, Entwisle J, O’Brien M, O’Byrne K, Thomas G, Snee M, Spicer J, Landau D, Lang-Lazdunski L, Bliss J, Peckitt C, Rogers S, Marriage Nee Denholm E, Coombes G, Webster-Smith M, Peto J. The Mesothelioma and Radical Surgery randomised controlled trial: The MARS feasibility study. J Thorac Oncol 2009;4(10):1254-8.
Tan C, Gleeson F, Treasure T.  Malignant pleural mesothelioma. In: Hunt I, Muers MM, Treasure T, eds. ABC of Lung Cancer, pp 25-8. WileyBlackwell, April 2009.
Treasure T, Tan C, Peckitt C, Entwisle J, Waller D, O’Brien M, Bliss J, Peto J. Mesothelioma and Radical Surgery trial (MARS): the feasibility study process. Lung Cancer 2009;63(Supplement 1):S26.
Utley M, Gallivan S, Jit M, Paschalides C, Tan C, Treasure T. Can patients progress modeling inform the management of cancer patients? In: Brailsford S, Harper P, eds. Operational Research for Health Policy: Making better decisions. Proceedings of 31st Annual Conference of the European Working Group on Operational Research Applied to Health Services, pp 243-252. Oxford, UK, Peter Lang, 2008.
Tan C, Treasure T.  UK surgical trials in mesothelioma. Lung Cancer in Practice 2007;3(2):8-9.
Pai V, Gangoli S, Tan C, Rankin S, Utley M, Cameron R, Lang-Lazdunski L, Treasure T. How best to manage the space after pneumonectomy? Theory and experience but no evidence. Heart Lung Circ 2007;16(2):103-6.
Tan C, Treasure T, Browne J, Utley M, Davies CW, Hemingway H. Seeking consensus by formal methods: a health warning. J R Soc of Med 2007;100(1):10-4.
Davies A, Tan C, Paschalides C Barrington SF, O’Doherty M, Utley M, Treasure T. FDG-PET maximum standardized uptake value is associated with variation in survival: Analysis of 498 lung cancer patients. Lung Cancer 2007;55:75-8.
Faith A, Peek E, McDonald J, Urry Z, Richards DF, Tan C, Santis G, Hawrylowicz C. Plasmacytoid dendritic cells from human lung cancer draining lymph nodes induce Tc1 Responses. Am J Respir Cell Mol Biol 2007;36:360-7
Tan C, Treasure T, Browne J, Utley M, Davies CWH, Hemingway H. Appropriateness of VATS and bedside thoracostomy talc pleurodesis as judged by a panel using the Rand/UCLA appropriateness method (RAM). Interact Cardiovasc Thorac Surg 2006;5:311-6.
Tan C, Sedrakyan A, Swift S, Browne J, Treasure T. The evidence on pleurodesis for malignant effusion: a systematic review. Eur J Cardiothorac Surg 2006;29:829-38.
Treasure T, Tan C. Cannabis, pneumothorax and lung bullae: author’s reply. J R Soc Med 2006;99(4):170.
Treasure T, Tan C. Miss, Mister, Doctor: How we are titled is of little consequence. J R Soc Med 2006;99(4):164-5.
Treasure T, Tan C, Lang-Lazdunski L, Waller D.  The MARS trial: mesothelioma and radical surgery. Interact Cardiovasc Thorac Surg 2006;5:58-9.
Tan C, Treasure T.  Radical Surgery for mesothelioma. International Pleural Newsletter 2006;4(1):1-2.
West D, Tan C. Thoracic surgery: new training for an old specialty.  BMJ Career Focus 2006;332:6-7.
Tan C, Treasure T. Mesothelioma: time to take stock. J R Soc Med 2005;98:455-8.
Lang-Lazdunski L, Tan C, Treasure T. Extrapleural pneumonectomy for malignant mesothelioma: should pericardium be resected routinely? J Thorac Cardiovasc Surg 2005;129(5):1202.
Alphonso N, Tan C, Utley M, Cameron R, Dussek J, Lang-Lazdunski L, Treasure T. A prospective randomized controlled trial of suction versus non-suction to the under-water seal drains following lung resection. Eur J Cardiothorac Surg 2005;27:391-4.
Tan C, Sedrakyan A, Treasure T. Pleurodesis for malignant effusion: time to stop using bleomycin? World J Surg 2004;28(8):253-4.
Tan C, Treasure T. Pleural adhesions: more friend than foe. Adhesions 2004;6:23-4.
Tan C. Pleurodesis for malignant effusion. In: Treasure T, Hunt I, Keogh B, Pagano D, eds. The evidence for cardiothoracic surgery, pp 119-30. tfm Publishing Limited, 2004.
Tan C. The management of (spontaneous) pneumothorax. In: Treasure T, Hunt I, Keogh B, Pagano D, eds. The evidence for cardiothoracic surgery, pp 107-18. tfm Publishing Limited, 2004.
Ang KL, Tan C, Hsin M, Goldstraw P. Intrapleural tumour dissemination after video-assisted thoracoscopic surgery metastasectomy. Ann Thorac Surg 2003;75:1643-5.
Tan C, N Alphonso, D Anderson, C Austin. Mediastinal haemangiomas in children. Eur J Cardiothorac Surg 2003;23:1065-7.
Treasure T, Swift S, Tan C.  Radical surgery for mesothelioma: How can we obtain evidence?  World J Surg 2003;27:891-4.
Tan C, Swift S, Gilham C, Shaefi S, Fountain W, Peto J, Treasure T. Survival in surgically diagnosed patients with malignant mesothelioma in current practice. Thorax 2002;57iii:iii36.

Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma revisited: the Australian experience

A discussion of and link to the Yan et. al (2011) article, “Improving survival rates after surgical management of pleural malignant mesothelioma: an australian institutional experience” as part of a series of posts on mesothelioma and extrapleural pneumonectomy (EPP).

A recent study by Yan et al. (2011) conducted at the Royal Prince Alfred Hospital in Sydney, Australia does more than look at the outcomes of the aforementioned treatment for malignant pleural mesothelioma.  This study, involving 540 patients, over 25 years also gives us a primer on the evolving treatment therapies for this condition.  As newer treatment therapies emerged, these therapies were given to eligible patients, starting with extrapleural pneumonectomy itself, in 1994 and extending to include both radiotherapy and chemotherapy. Chemotherapy consisted of a combination of pemtrexed, carboplatin and cisplatin.  While this alters the results significantly it also provides for an interesting introspective on the treatment of malignant pleural mesothelioma.

This study is noteworthy for both this reason, and as a study looking at a larger set of patients than many of the other studies on this topic.

Study Design: consecutive, non-randomized.

Patient population:  540 patients; organized into two groups for statistical analysis.  Group I – 270 patients (consecutive patients from March 1984 to September 1999.)  Group II – consecutive patients September 1999 to Jan 2008.  As the authors noted, due to the rarity of this condition in Australia, it took 25 years to recruit 540 patients for treatment.

Patient characteristics: the vast majority were male (455 patients)  with a mean age of 66 (+/- 11 years).  315 patients with right-sided disease, the remaining 225 with left-sided disease.

Disease subtypes:

235 patients with epithelial subtype, 212 with sarcomoid/ biphasic  (type determined by tissue pathology)

Treatments received:

69 patients had extrapleural pneumonectomy

269 patients received pleurectomy/ decortication

202 patients received pleurodesis

62 patients received post-operative radiotherapy starting 8 to 12 weeks after surgery. This treatment was added in 2002.

65 of the patients received adjunctive chemotherapy

Notably, as mentioned above, there was a distinct difference in the treatment allocation for groups I and II due to changing treatment protocols, and the development of new therapies.  While 22% of patients in group II received EPP, only 5% of patients in group I received the same surgical procedure.

Treatment strategies were also limited by patient factors; namely the patient’s physical condition / functional status as being considered able to withstand the proposed treatment therapy.  As mentioned in a previous post, extrapleural pneumonectomy is an extensive surgical procedure which requires significant patient reserves and pre-existing functional abilities for anticipated recovery.  In frail or debilitated patients, (as defined by criteria set forth by Yan et. al) EPP was not attempted.  Some of these patients received either pleurectomy with decortication.  In patients deemed too fragile to withstand either of these procedures, a talc pleurodesis (either by VATS or tube thoracostomy) was performed as a palliative procedure.  Unsurprisingly, the patients receiving palliative treatment options had shorter median survival periods.

Results:

18 patients died in the perioperative period, including 3 EPP patients.

Median follow-up period for the study was ten months.  At the time of follow-up the majority of patients (433 patients, 80%) had died with a median survival time of nine months for group I (range 0 – 115 months).

In group II, the median survival time was 13 months.  (range 0 – 72 months).

Long term survival by group:

Group   I                                                  Group II

1 year      35%                                                     50 %

2 year     16%                                                     22%

3 year       9 %                                                      12%

5 year        2 %                                                       9 %

These five-year survival rates highlight the importance of continued studies for the advancement of treatment therapies for this condition.

Factors associated with greater survival:

In reviewing their research, the authors were able to identify four independent factors that increased the likelihood of survival in this population. (See original article for discussion in further depth.)

1. Yan et. al found that the epithelial subtype was more favorable for patient survival, and that this subtype was more common in the patients in group II.

2.  The surgeon’s experience (of greater than 100 cases) was positively correlated with greater survival.  Surgeon expertise has been shown to be a factor for better patient outcomes in multiple procedures.

3. Patients who received EPP had improved survival compared to patients who received other treatments.  However, this also reflects a selection bias, since the patients who were eligible for EPP had better pre-operative functional status than patients who received other treatments.

4.  Premetrexed chemotherapy – patients who received this chemotherapy regimen had greater survival.

blog author’s note:

Despite dismal five year survival rates for treatment of malignant pleural mesothelioma by a multitude of treatment methods, extrapleural pneumonectomy (with adjuvant chemotherapy) appears to be the most effective cytoreductive surgery for this condition. ( As noted in related posts, HITHOC is an emerging therapy that combines the principles of both.) We will continue to follow research in these areas for the treatment of malignant pleural mesothelioma and invite the experts to add their comments.

Original article:   Yan, T. (2011). Improving survival rates after surgical management of malignant pleural mesothelioma: an australian institutional experienceAnn Thorac Cardiovasc Surg 2011; 17: 243-249.  Primary author: Dr. Tristan Yan.

HITHOC in Regensburg, Germany at the University Medical Center

Information about the Thoracic Surgery program at the University Medical Center in Regensburg, Germany – and their research into HITHOC.

After sending out several emails to multiple facilities with published research on HITHOC – Dr. Michael Ried of the University Medical Center in Regensburg, Germany responded with some interesting information about the thoracic surgery program at his facility, led by Dr. Hans Stefan Hofmann (who was cited in previous posts) and is the primary author of an article in German, called “Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion.”

Dr. Ried reports that surgical treatment of thymoma and malignant pleural mesothelioma are two of the procedures their department specializes in.  Since 2008, they have been performing HITHOC in these patients in combination with pleurectomy and decortication.

Dr. Reid reports that they will be publishing the results of a prospective study based on their experiences with HITHOC in the near future.

Contact information/ Program Summary details:

(note – site is entirely in German, no English version)

University Medical Center:  http://www.barmherzige-regensburg.de

Department of Thoracic Surgery:  http://www.barmherzige-regensburg.de/thoraxchirurgie.html

Chief of Thoracic Surgery: Dr. Hans Stefan Hofmann

General Contact information – department of thoracic surgery:  http://www.barmherzige-regensburg.de/1772.html?&L=0

Email: thoraxchirurgie@barmherzige-regensburg.de

I’ve included visible link information for your information.  Google translate will translate the website, as needed.

I have requested some additional program information, and will update this page, as soon as I receive it.

Additional Resources:

Dr. Hofmann is primary author on more than 40 journal articles on thoracic surgery topics (in English) – several dealing with lung cancer on a cellular level.  I have posted just a very small sample of citations here that I have selected among full text articles available on-line. (Names of articles may have been changed).

1. The wind of change in the therapy of lung cancer – in this free full-text article from 2006, Dr. Hofmann talks about the future of treatment for lung cancer.

2. The DNA of lung cancer – this article talks about specific DNA markers for aggressive lung cancers, and how these markers may be useful in targeting / treating disease.

3. Diagnosing lung cancer with DNA

4. While Dr. Hofmann is not the primary author on this article about treating a soldier wounded in Afghanistan with artificial lung therapies  – I thought it dovetailed nicely with our recent discussions on artificial lungs/ ecmo and ecmo-like therapies and future developments etc.

Latest research findings: Mesothelioma

new research results from the University of Pennsylvania on the treatment of pleural mesothelioma.

The University of Pennsylvania reports the latest results of a small study involving 28 patients with pleural mesothelioma.

This limited study compared combination treatment using photodynamic therapy along with a lesser lung surgery (14 patients) in comparison to extrapleural pneumonectomy alone (14 patients).  22 of the 28 patients also received chemotherapy.

Patient population: 28 patients – 12 /14 patients in either group with advanced (stage III/IV ) disease

Results:  Extrapleural pneumonectomy group had a median survival of 8.9 months.  The combination photodynamic/ surgery group median survival exceeded two years (when the study ended).

Take away message for readers:  It’s too early, and the study groups are far too small for us to generalize these findings.  However, these preliminary results are encouraging and should prompt more, larger scale studies / trials looking at photodynamic therapy as adjuvant therapy along with thoracic surgery for pleural mesothelioma.

 

Update: 06/15/2011:

the mesothelioma study from PA just got picked up by a major wire service, so expect to read and hear a lot more about it.

Update: 08/15/2014:  Mesothelioma.net has asked that I link with their site.  They offer some informational services for people facing mesothelioma.  Please let me know if this site is spam-plagued or otherwise dubious and I will remove the link (the site is a bit ‘shiny’ and circular for my taste.)

Extrapleural Pneumonectomy: EPP

Extrapleural pneumonectomy for malignant mesothelioma

Extrapleural Pneumonectomy (EPP) is a radical operation in which the entire lung, and tissues of the lung space (pleura, diaphragm and pericardium) are removed.  This is done as part of a cancer operation, often for an aggressive cancer called malignant mesothelioma. During cancer operations, surgeons have to remove all or as much cancer tissue as possible, including microscopic cells that are not visible to the surgeon at the time of surgery.  Any tissue that is left behind may have cancer cells which will continue to grow, and spread.  Due to the location of the cancer cells (in the lining), surgeons have to remove more tissue than if the cancer was centered in the lung itself.  This includes replacing the diaphragm with a synthetic patch during surgery.

Mesothelioma is named after the cells it affects.  These mesothelial cells make up the “linings” of the body cavities.  For this reason, mesothelioma can affect other areas of the body, in the linings of the abdomen called the peritoneum, the pericardium (the lining around the heart), and most commonly, the pleura.

Inside the chest, coating the chest wall is a thin lining tissue called the pleura.  The interior area of the rib cage and chest are thus called the pleural cavity.  When mesothelial cancer cells invade this fragile tissue layer, it is called pleural mesothelioma, which is different from peritoneal mesothelioma.  (Peritoneal mesothelioma affects the peritoneal cavity, or abdominal cavity.)

Not everyone is a candidate for this surgery.  Due to the radical nature of this procedure, patients need to have good pulmonary function and overall functional status prior to surgery.  (The patient is going to lose one whole lung during this procedure, so patients that are already oxygen dependent / bedridden or otherwise debilitated won’t be able to tolerate this procedure.)  The best patients for this surgery (the patients who will have the best outcomes/ receive the most benefits from surgery) are patients with good functional status (able to perform normal activities of daily living) with earlier stages of the disease.  In these patients – this surgery can extend their lives significantly.  In patients with more advanced (stage III/ stage IV) disease, the surgery will make them live longer (months) but the quality of life may be worse post-operatively.

Prior to consideration for extrapleural pneumonectomy (or any other treatment) the doctors will want to definitively diagnose (prove the diagnosis through tissue biopsy) and do preliminary staging.  (Final staging occurs after the operation when further tissue / lymph node biopsies are evaluated by the pathologist).

Preliminary staging and pre-operative evaluation is the process to try to figure out how much cancer is present (has it spread?) and whether the patient can tolerate a large operation.  Mediastinoscopy; a surgical procedure to look at mediastinal lymph nodes (lymph nodes behind the sternum or breast bone), PET scans and blood for tumor markers help determine how much cancer is present.  The tumor markers also help the oncologists figure out which chemotherapy drugs will work the best.

Pre-operative testing is looking at lung function, to see how well the patient will do with only one lung.  Cardiac testing may be done as well since surgery can be stressful to the heart.

If the disease is controllable with surgery, and the surgeon thinks the patient can withstand surgery – the surgeon will consult with an oncologist about the timing of surgery and adjuvant treatments (chemotherapy/ radiation).

Even with radical surgery, the prognosis for malignant pleural mesothelioma is poor, but improves with combination therapies (surgery with chemotherapy/ radiation.)  Currently, surgeons are investigating the use of cytoreductive hyperthermic chemotherapy  (HIPEC/ Hithoc) for treatment of pleural based mesothelioma.  (Previous studies by Dr. Paul Sugarbaker has shown this treatment to be effective with advanced abdominal cancers including malignant peritoneal mesothelioma.)  We will discuss HIPEC further on a future post.

There are numerous studies looking at extrapleural pneumonectomy for treatment of malignant pleural mesothelioma. The links below is just a small sampling.

1. Extrapleural pneumonectomy for malignant pleural mesothelioma (2005) – Argote- Greene, Chang, and Sugarbaker. (Note: this article was co-authored by Dr. David Sugarbaker, Department of Thoracic surgery, Brigham Womens & Children’s, not Dr. Paul Sugarbaker, developer of HIPEC.  I am going to attempt to contact Dr. Davis Sugarbaker for commentary for the site since he is the expert on this topic, so hopefully I’ll be able to update the site with his post in the future.

2.  Radical surgery for malignant pleural mesothelioma – Japanese study comparing results for EPP versus pleurectomy / decortication.  The main points to take away from this study is that stage of disease has a huge impact on prognosis, and outcomes after surgery.  (The patients with stage I and II that underwent EPP did fairly well.)

3. Review of 83 cases of EPP – (2009) French study which unintentionally highlights the potential complications of surgery of this magnitude(almost 40% had major complications and had a re-operative rate of almost fifteen percent.)