“The Chinese Method” of Intermingled Skin Grafting in severe burns: long term results, genetical aspects and potential use in burn disasters and difficult public health settings

Summary

Objective:
Analysing the method´s actual interna-tional relevance and potential use in Disaster Medicine and difficult public health settings, this article also presents genetical late results of one case 30 years after Intermingled Skin Grafting.

Materials and method:
The traditional Chinese Method of Intermingled Skin Grafting (ISG), is an almost unknown technique to western burn surgeons. It is performed using a special arrangement of a mixture of cadaver and autologous skin on severe burn wounds.

Results:
The method proves to be highly effective in lowering lethality rates especially in the most severe cases of over 80 % burned body surface, and even when compared to modern-day tissue engineered skin replacement materials.

Conclusion:
These results clarify the final outcome of the so called „Sandwich Phenomena”, observed in the Chinese Method.

Key words:
Severe Burns, Skin Transplants, Autologous Skin, Cadaver Skin, Lethality Rate, Genetics, long term outcome, Di-saster Medicine, Public Health, Review, Case report.

Introduction

Severe burns, especially large body surface area burns have been and still are a serious threat to human life. For a long period of time there was no proper way to replace large areas of lost skin to burn trauma. This resulted in high lethality rates while progress in perioperative medicine (EMS, Intensive Care, Anaesthesiology) only shifted the time of death form the early phase towards the late phase. Surgery however was trapped in the quest for the ideal skin substitute for decades and somehow still is. This quest has however lead advancement in the Western World to the creation of so called “tissue-engineered materials” (synthetical, bio-synthetical and cell-cultured Skin Replacements). These high-tech inventions have proven their value in many cases, but on a downside demand enormous financial input and a very high standard in technological advancement. This basically excludes a large portion of people in so called developing countries from this form of treatment [12].

The Chinese Method of Intermingled Skin Grafting, a Review of the Literature

In the 1950`s Chinese scientists tried to reproduce the results of Mowlem and Jackson [2]. The findings of Mowlem and Jackson suggested that cadaver transplants on burn wounds would not be generally rejected but rather undergo a repeated desquamation while fresh autologous skin would be restored on the wound bed in the process. The Chinese experimented with various patterns and finally discovered one type of arrangement that will within short time fusion both skin parts. They also observed a repeated desquamation but even more witnessed an internalisation of cadaver skin into the deeper layers of the autologeous skin bed while the whole mixed/intermingled transplant underwent the fusion into a permanent skin replacement (Sandwhich-Phenomenom). However these findings of the Chinese Scientists were made during a time of self-isolation of the whole country - the cultural revolution - and therefore not published in western journals, alas the world was unaware of them. The Chinese published their results and kept making constant scientific progress on their findings, but alas these publications only appeared in Chinese Journals [23, 24, 25]. These first few writings name no specific author, but in the sense of Communism the 2^nd Medical Military Hospital (Shanghai) was credited.

In the late seventies however the “word started to spread” around among experts that in China marvellous progress in the treatment of severly burned cases was made, but the knowledge transfer between China and the West was restricted to personal contact, good fortune or individual effort. Domres brought the method of ISG to Germany learned of the method first hand by scientific exchange between him and Yang in China [8], while repatriating a German Official from China to Germany. During his visit to China the transport of his patient was delayed and only by personal interest and good fortune he visited Yang at the 2^nd Military Hospital and learned about the method first hand. He then informed the scientists around Koslowski (Hettich, Kistler) about the Chinese discoveries and this group of scientists would soon remarkably progress the German and Western efforts to research and understand the histological and immunological proceedings in intermingled skin transplants [14, 15, 16]. Their publications alone count for the majority of all publications from westerners made in western journals. They even went so far to develop an early computer driven mechanical device to facilitate the laying pattern of ISG [10]. The real kick-off for broad international interest in the method however were Yang`s publications [16, 21] which echoed in a broad international response. However by 1990 the once „hot topic” almost vanishes from the international scene, although Publications still exist and have been regularly published over the last 15 years these more recent publica-tions are however once again mainly of Chinese origin, and to make things „worse” once again are mostly published in Chinese-only-speaking journals. As a result modern-day western burn medicine seems to have forgotten the Chinese Method.

The sandwich Phenomenom and its long-term outcome

Part of the Method`s success is ironically the greatest threat of life of the severly burned. The immune-dysfunction that these cases suffer from makes them vulnerable to SIRS and sepsis, which in turn makes the severely burned prone to multi-organdysfunctioning and in the end to death [4, 19]. This immunological condition on the other hand allows cadaver skin to survive a prolonged time [19]. However when the immune system recovers allogenic skin is rejected. Cytokines are well known to indicate the state of the immune system and a prognostic factor for the final outcome. A Chinese experiment in rat [6, 11, 16] observed intermingled skin grafting alternating Interleukin Levels differently than in purely singular (autologous, cadaver) transplantations. In intermingled transplants Interleukin levels in allogeinic and autologous skin probes converged to comparable concentrations with better prediction rates for survivability. This implements a change in antigenecity and might be the reason for the missing general rejection of cadaver skin tissue even after recovery of the immune system.

As a result one can observe a process of transformation during ISG which is called “sandwich phenomena” by Chinese authors. What can be seen is that the autologous dermis creeps underneath the allo-epidermis, while literally lifting it off the wound bed [9, 10]. The allo-dermis is then “sandwiched” between the autologous wound bed underneath and outgrowing autologous skin atop. Three months after transplantation the histological picture shows the remaining cadaver skin already being reduced to a thin layer. This can be observed in the following case report:

Case Report

In 1982, during a military conflict in the Laghman province of Afghanistan, the 21 years old male (A.Q) sustained severe burn injuries as a result of a blast in a petrol-tank. Immediately taken away from the battlefield, he received the treatment available in that environment for a period of 6 months. After this period he was brought across the border to the Afghan Surgical Hospital in Peshawar, Pakistan.

When he was admitted there his survival prognosis was very low. A.Q. had full thickness burn wounds of nearly 50% of the body surface, who discharged foul smelling, greenish puss. His muscles were considerably wasted and atrophired and he was unable to extend either of his knees. He received then the classical treatment for burn injuries: He got an isolated room kept as antiseptic as possible, and his wounds were exposed to air, dressed as and when indicated. Furthermore sufficient rations of fluids, local and general antibiotics, pain killers and other appropriate drugs were given to him, as also as ten pints of blood. In a second treatment series by a plastic surgeon at the Government Leady Reaning Hospital, Peshawar A.Q.’s burn wounds were of and on dressed and skin grafts were done according to a gradual and successive schedule. During this period almost 20 pints of blood were transfused to the patient, he got antibiotics and analgesic/phlogestics etc.

But regretfully all these attempts ended in a vain. Most of the skin grafts got rejected and the A.Q.’s general condition deteriorated. It was then in 1983/84 when he was transferred for treatment to the University Hospital in Tübingen Germany.

The third degree burn wounds were still unhealed and infected with an extension of 40–50 % of the patient’s body surface. His left knee joint was bend in a contracture due to a deep burn wound. Furthermore the patient had an extreme kachexia with hookworm strike, urinary bladder stones and ongoing diarrhea, as also as an eardrum perforation on the right.

After a high-caloric infusion-pretreatment and a so far normalization of the metabolic situation, as well as the restoration of a normal bowel function under Vermox-therapy, the patient was able to receive his debridement of the left knee joint and stabilization of an external fixator (Fig. 5). Following this the first skin transplantation started.

Thereby, in preparation for an intermingled skin grafting, the patient’s burn wounds were covered with fresh allograft skin, from which little squares of approximately 0.5cm² were cut out, according to the above described technique.Three days later, after a starting revitalization of the allografts, the patient receivethe second skin transplantation. Within this the cut out square-holes of the allograft skin were covered with autologous split-thickness skin-islands of the same size, taken from the patient’s head. Although the patient’s general condition was still not optimal the operation was successful so far.

According to the persisting infection a small part of the transplants was not taken and covered by a third skin transplantation one month after the second one. During this autologous split-thickness skin-islands were taken once again from the patient’s head to cover the cnterpart cut out areas of allograft skin.

About 15 months after his admission A.Q. was able to walk independent, only with one hand-stick and perform basic daily duties on his own. Today he lives in Pakistan, is married, has two children and works as a tailor.

To define the genetical identity of A.Q.`s body surface, a MicroSatellite-Analysis of skin probes was conducted. The results show the following:

The vast majority of the skin probes (>90%) were genetically identical. A minute-chimerism however couldn’t be ruled out. Still the results strongly suggest an identical person and thus a complete fusion of the various parts of the transplant.

Discussion

The main characteristic of the Chinese Method is the improvement of survival rates in general, but especially for the most severe cases of burned patients with over 80 % burned body surface.

Kistler during the 1980`s observed that since the introduction of ISG the survival rates of burned patients in China significantanly improved:

A comparative study [13] of a Chinese (SMMU) and a Japanese Hospital (NDMC) in 2005 validated Kistlers obersvation (18) proved Kistler`s observation in recent years. According to the findings of the Literature review, the authors of this study mentioned that ISG is unknown in Japan [13], which after all is a neighbour of China.

Comparison of the survival rate based on the burn surface area between the two hospitals. The survival rate of the pa-tiens at SMMU hospitál exceeded that of the patiens at NDMC hospital based on the burn surface area, especially in patiens with a TBSA of greater than 80 %. We show the number (survivors/patients) which was used to calculate the survival rate on each column bar.

Comparison of the survival rate based on the burn index between the hospitals. The survival rate of the patiens at SMMU hospital exceeded that of the patiens at NDMC hospitál based on the BI, expecially in patiens with a BI of greater than 60. We show the number (survivors/patients) which was used to calculate the survival rate on each column bar.

These results are remarkable. Even more so since the necessary technical requirement to achieve them are just basic surgical equipment, a readily available source of cadaver skin and and comparable small amount of autologeous skin - thus making the method very cost effective. However cadaveric skin is a non-body-own transplant and needs to be scanned for infections and other illnesses before using it [19]. Unless no other option, some storage and testing technologies therefore have to be at hand. If the risk of viral and bacterial transmission is neglected, even the use of fresh cadaver skin is possible. Cadaver skin, in worst case-scenarios such as disasters, might serve as an early available and highly valuable. Material which is easily accessible. Using cadaver skin however also has ethical aspects. It is simply not acceptable in all cultures [7]. Variations of the Chinese Method without Cadaveric Skin are possible. The usage of close-relative`s skin. [3, 21] or xenografts (e.g. Pig Skin) [5] has been successful using intermingled transplant-pattern.

The Chinese Method however leaves a permanently visible mark on the Patients skin texture by alternation natural pigmentation.

Conclusion

The Chinese Method - life-saving, cost-effective, almost no technical requirements, readily available – seems highly considerable as an option for the treatment of even the most severly burned cases. This is even more so the case in countries with difficult public health settings and especially in (Burn) Disaster Situations. Knowledge and the potential ability to use the method is highly advisable for Medical Disaster Teams dispatched to internal Burn Disasters.

Author’s note

Special thanks goes to Prof. Dr. med. P. Bauer from the Institute of Medical Genetics and applied Genomic, University Clinic Tübingen for the genetical analysis presented and to Dr. med. G. Metzler from Department of Microscopic Histology of the Dermatological University Clinic, from the University Clinic Tübingen for the histological contribution presented in this publication.

Prof. Dr. Dr. Bernd Domres

bddomres@yahoo.de