Macchiarini’s patients, the real situation

Paolo Macchiarini, former star surgeon at Swedish Karolinska Insitutet (KI), came back to Sweden to give his version of the events, about the failed tracheal transplants he performed, and some other things. He had two core messages: he extended the lives of the dying patients by transplanting them with untested plastic tracheas, and he did all this certainly not behind everyone’s back, but with full knowledge, approval and supervision of his colleagues at KI.

Macchiarini’s interviews can be read at the medical newspaper Läkartidningen, the tabloid Expressen and the most interesting one was with the TV channel SVT (which previously aired the documentary Experimenten, which kick-started the scandal).

Update 23.05.2016 Macchiarini’s SVT interview from May 4th was transcribed by the KI whistleblowers (who also highlighted those in their views most untruthful passages in red). With the permission of the SVT interviewer Nike Nylander I am making the transcript available here.

The interviews focussed around the plastic “stem cell”-regenerated tracheas Macchiarini implanted into 8 patients. The first recipient, Andemariam Teklesenbet Beyene, was operated in 2011 and died two years later, after the implant came loose. On SVT, Macchiarini now claimed Beyene’s life expectancy was less than 6 months, and the operation was approved by a “multidisciplinary team” at KI and the Karolinska University Hospital. The material was tested as safe, insisted Macchiarini. Not as trachea in the unsterile airway environment, but in other setups, such as blood vessel surgery, he declared. This synthetic trachea scaffold was manufactured by the lab of UCL nanotechnology professor Alexander Seifalian, later on by the US company Harvard Apparatus under a shared patent with Macchiarini (as I reported here).

According to documents available on RetractionWatch, Beyene was operated by Macchiarini because of a recurrent tumour after radiotherapy. However, there was never any biopsy that proved this tumour recurrence, it showed the tissue to be “without signs of malignancy”. Even the tracheal segment removed in the process of transplantation was not sent for pathological examination. This means, Macchiarini is accused to have removed a non-cancerous trachea to replace it with plastic one, while pretending to be saving the patient Beyene from deadly tracheal cancer.

Macchiarini’s US patient Chris Lyles had mucoepidermoid carcinoma of the trachea. Since a large segment of his windpipe was affected, a resection was not a medically viable option. Instead of radiation therapy applied in such cases, Macchiarini decided to remove Lyles’ trachea anyway and inserted a plastic “regenerated” one. Lyles died only four months after the operation, not really a life extension as announced by Macchiarini on Swedish television.

In regard to his operation at the Kuban State University in Krasnodar, Russia, on Yulia Tuulik, who did not appear terminally ill at all (according to all available evidence) to justify an experimental plastic trachea transplant, Macchiarini kept disagreeing. To him and his Russian colleagues, Tuulik was gravely ill, though he refused to specify what exactly was threatening her life so badly. Also here, Macchiarini insisted that the decision to operate this patient was made by 30 medical professionals in a videoconference (list of the participants, including those from KI, available here). Tuulik died two years after the operation, on SVT Macchiarini seemed to agree that the plastic implant was indeed too short and should not have been used. In any case, most patients died of other causes than his trachea transplants, as Macchiarini argued on Swedish TV. He refused however to go into details here as well. In fact, his Krasnodar collaborator Igor Polyakov claimed in the Russian media (with his word as only evidence) that the second plastic trachea recipient Alexander Zozulya died in a bicycle accident, allegedly fully recovered thanks to the operation he and Macchiarini performed. One would not be surprised if Polyakov claimed Tuulik and others also died in a mountaineering expedition after a bear attack.

Remarkably, even after 8 largely lethal transplants, Macchiarini was not able to take a stand on whether his plastic tracheas worked or not. His indecisiveness went so far that he could not even reply with yes or no when asked: “Are you a pathological liar?”

Macchiarini’s key defence is shared responsibility. Indeed, there is plenty evidence to support this. His recruitment was recommended in a letter to KI’s then-rector Harriet Wallberg from June 4^th, 2010, signed by 14 KI scientists, including world renowned stem cell researchers Urban Lendahl and Ernest Arenas (available here). Some of these other co-signers, the key KI otolaryngologists Li Fällender-Tsai, Lars-Olaf Cardell and Mats Holmström soon became concerned about the accusations of fraud and extortion Macchiarini was facing in Italy. No, not in the way as to reconsider his recruitment to KI. Quite the opposite. The trio wrote in September 2010 to Macchiarini’s close supporter and newly elected president of Tuscany, Enrico Rossi, asking for a letter of support for Macchiarini and for his idea of the “European Centre for Advanced Regenerative Airway Surgery, involving Stockholm, London and Florence”. This Rossi eagerly did. In his letter from September 20^th, Rossi complained that “Prof. Macchiarini has been as subject of a vile attack by the local media in Florence” and that University of Florence failed on its promise to grant an exceptional professorship to Macchiarini (some details on this given in an open letter by Sergio Romagnani, Professor Emeritus of the University of Florence). Rossi declared:

“I am ready to assume every necessary political and financial effort, as well as encouraging the support of the academic community. […] Prof. Macchiarini’s integrity and morality has never been questioned, nor has his professionalism and achievements. His conduct has always been exemplary and we wish to intensify his collaboration with us. […] Prof. Macchiarini is one of the most talented minds this region ever had and we will support him in achieving his goals through whatever means he chooses”.

For the Florentine Careggi hospital, its director Edoardo Majno also provided a letter of support for Macchiarini’s idea of the European Airway Institute on January 15^th 2011. It was addressed to Rossi, leaders of KI and UCL as well as Great Ormond Street Hospital in London.

The entire above communication is available exclusively here.

With such stellar support, one can almost understand why rector Wallberg signed the recruitment of Macchiarini in October 2010. Especially since back then, but even now, his first breakthrough trachea transplant in Barcelona in 2008 was deemed a full success.

As I previously reported, the patient Claudia Castillo received a first “stem cell” regenerated donor trachea, seemingly before any studies in animals in this regard were even done. The relevant animal experiment manuscripts were submitted for publication almost a year after patient Castillo got her trachea transplant from Macchiarini and his UCL collaborator Martin Birchall.  Of course it is possible that Macchiarini’s team for some unfathomable reason chose to hold back publishing the results of previously completed animal studies before operating a human being. The ethic vote in Barcelona might have been granted based on unpublished results. However, these earlier animal experiments would still have been registered with the University’s animal research ethics committee. Yet neither there, nor at the Office of Research Management of University of Barcelona was I granted even an acknowledgement of the receipt of my email, despite my insistence.

But regardless of all this, what is the condition of the patient Castillo? Unlike Macchiarini and his supporters claim, she is not doing very well. Pierre Delaere, the thorax surgeon from KU Leuven, forwarded me this

“inside information from treating doctors in Barcelona 28/4/2014: No graft found, serious complications, need for a pneumectomy but still reported as a major success by Macchiarini and Birchall!! We tried to approach Dr Molins and Dr Gimferrer at several occasions since 2014 without success”…

In fact, there never was a full trachea transplant, and even that lacks any lining epithelium and has collapsed despite continuously present stents, as the doctors reported:

“In fact, this is not a real tracheal transplant, because only left main bronchus was replaced by a donor segmental tracheal homograft. This graft has remained open 5 years because of the insertion of multiple biodegradable stents”.

The document is available exclusively here. The patient Castillo now needs to have her left lung removed, which is scheduled to happen this month or in June, as I was reliably informed. This patient’s tragedy is apparently not any of The Lancet’s business, where the ground-breaking operation and the 5-year follow-up study was published, presenting her as fully recovered. The journal prefers to disregard her medical records, until the ongoing KI investigation instructs them how to proceed.

According to Delaere’s information, also the second “regenerated” donor trachea recipient, Ciaran Finn-Lynch, operated at Great Ormond Street Hospital for Children in London, could only survive so far due to a permanently present stent which kept the transplant open. His current condition is unclear, as no information is being released.

Update 20.05.2016: Swedish magazine Filter now reports what happened to the first patient Macchiarini operated as newly recruited KI professor. Zjadyra Iglikova, a victim of traffic accident, received in December 2010 in Moscow a “regenerated” donor  trachea transplant and was declared as “fit and healthy” and full success. The journalist  Johannes Wahlström however found out, the cadaver trachea transplant had to be urgently removed after only a few days, and patient Iglikova was returned to tracheostomy. In early 2016, her family informed the reporter of the true conditions of this patient of Macchiarini’s: she was dying.

However, before his first “success”-patient Castillo, Macchiarini tried partial trachea replacement in a German patient in Hannover, where he used to operate as Head of the Lung Clinic at the Heidehaus hospital. The local newspaper, Hannoversche Allgemeine Zeitung (HAZ) reported on September 6^th 2003 that Macchiarini operated the cancer patient Ernst Fromhage by transplanting into his trachea a patch of decellurised pig intestine seeded with patient’s own muscle cells.  Macchiarini also published this experiment, which was harshly criticised, also because of the high risk of infection, by the famous late thorax surgery specialist Hermes Grillo. I tried to find out more about this operation from 2003 and the status of the patient Fromhage, but the PR-person at the KRH Klinikum Region Hannover (which integrated the Heidehaus), Petra Kesten-Kühne, told me:

“Unfortunately we are not aware of any details about this surgery or of other such operations. Same applies to this former patient”.

On the phone, Kersten-Kühne promised me to at least to try and locate these files, but I have not heard from her since. Update 1.12.2016: While investigating the trachea transplants of former Macchiarini collaborators Heike and Thorsten Walles, I found out that the patient Fromhage died 16 months after the operation.

Macchiarini’s behaviour at Heidehaus in Hannover was not always exemplary. In 1999 their leading surgeon fell through the specialist exam (Facharztprüfung), yet succeeded at the second take in 2000. Subordinate doctors had to suffer from Macchiarini’s leadership style, several assistant physicians complained to the German Medical Association about being personally insulted by him. Against his colleague Mahdi Kadry, Maccharini allegedly led a campaign of mobbing and defamation until Kadry was forced to leave the Heidehaus. Even patients had to live with the consequences of Macchiarini’s feud with Kadry. The newspaper HAZ reported in April 2004 about an altercation at an “open patient”:

“Mahdi had operated the patient six days earlier and replaced part of his abdominal aorta. The patient complained afterwards about pain. A thrombus had formed inside a vein near the site of the surgery. Kadry was about to operate the new problem area separately, when the chief physician Paolo Macchiarini appeared. The medical director opined to use a larger implant, which also included the already replaced part of the abdominal aorta. The two physicians could not agree. What followed was, according to Kadry’s lawyer Rolf Bartels, a “harsh confrontation”. Since the chief physician had the final say, he prevailed. The operation demanded by Macchiarini brought the patient into life-threatening danger, as the lawyer Rolf Bartels explained. Allegedly, the 51 -year-old patient lost several litres of blood during the intervention. Meanwhile, there he is well again. […] Particularly critical in this dispute was that Kadry was the only specialist in vascular surgery. Prof. Macchiarini does not have such a qualification”.

According to the information Macchiarini gave in the Swedish media interviews, he does not work in research anymore. He indicated however to be operating patients around the world. Under these circumstances, maybe these patients should consider asking for a second opinion, before going under Macchiarini’s knife.

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Please read also my follow-up article Claudia’s Trachea.