My CREDO for SCIENCE:

Spare time in life for science. Science in spare time of life

Short Summary

Theoretical, Experimental & Clinical Research 1979 - at present

• The unique phenomena have been observed and discovered in living substance which have become fundamental discoveries of importance to all of medicine. The discoveries are especially valuable for all of cryomedicine and cryoscience. The pioneering contributions represent a breakthrough in medical science, especially in cryoscience, cryomedicne, cryosurgery, and cryotechnology. It has been carried out crucial achievements in the rapid development of applications of medical importance. It has been done essential steps in the evolution of modern cryoscience, cryomedicine, and cryosurgery.
• For the first time, a number of theoretical and experimental studies, both in vitro and in vivo, have been performed to explain the action of low temperatures on tissue. The basic theoretical aspects due to the own theoretical studies are:
  new experimental model was developed for the investigation of the dynamic temperature field of the frozen zone and the definition of the four phases for the effect of low temperatures on living tissue
  
  investigations of the effect of freeze-thawing processes using temperatures of varying intensity from -40 °C to -180 °C by means of disc-shaped cryoprobes with diameters of 5 to 50 mm respectively, and a laparoscopic needle with a diameter of 10 mm in vitro
• For the first time, the scientific implication of the longstanding research clearly is to define that the early and late cryosurgical vascular changes and circulatory stagnation together with the following cryoaponecrosis and cryoapoptosis as well as cryosurgical anti-angiogenesis, are the main important mechanisms of living liver tissue damage as a response to the freezing-thawing process. These are the main mechanisms of biological living tissue injury following the low temperature exposure. Especially these mechanisms are well elucidated and illustrated at the lowest temperature of -180 °C. 
• Phenomenon “Cryogenic Protein Denaturation”. Here we discover a natural phenomenon and show for the first time the early and late ultrastructural cellular outcomes in hepatocytes after low-temperature exposure in vivo, using transmission electron microscopy. Immediately and one hour after freeze-thawing, hepatocytes display a disrupted plasma membrane, and mitochondria are observed with electron-translucent matrix and disrupted membranes. Electron-dense inclusions of denatured protein are also notably present. Immediately and 24 hours after the cryogenic procedure, full lysis of plasma membranes and the presence of picnotic nuclei are observed. Mitochondria with lysed matrix and disrupted external and internal membranes are once again observed, as are the denatured protein bodies. We regard as most significant our novel observation of intracellular cryodenatured protein inclusions. Such freezing-induced denatured protein bodies have not previously been reported in vivo. Further study of the prevalence and mechanism of this novel phenomenon of protein denaturation should provide the basis for a profound understanding of the effects of low temperatures on living structures, as well as the mechanisms of freezing injury and the pathogenesis of frostbite. This is the main mechanism of deciphering of low temperature impact on living matter in nature.
• Phenomenon "Lunar Eclipse". The effect of deep low temperatures on living matter has been deciphered in cryoscience and cryomedicine. The early and late ultrastructural cellular changes, which were presented by the exposure of low temperatures at -80 °C and -180 °C in vitro, refer to the fundamental pathogenetic mechanisms in living matter. The properties of the living biological structures response after deep low temperature exposure provide important insights into the mechanisms of damage and the cryogenic lesion after the freeze-thawing process in its different phases in the field of cryoscience and cryomedicine, i.e. cryosurgery.
• The early and late aseptic cell cryoaponecrosis with subsequent aseptic cryoapoptosis as well as cryosurgical anti-angiogenesis are the basic important mechanisms of living biological systems damage as a response to the freezing-thawing process. The early and late ultrastructural changes in living matter were especially pronounced at the temperature of -180 °C (P<0.001). The bacteriological results have not yielded any growth of microorganisms (P<0.001). Finally, the nano-structures of the living substance were fragmented and denaturated into smaller nano-particles following deep low temperature exposure, leading to the deep low temperature interitus of the living matter on a nanometric scale. 
• For the first time, the several experimental studies of the biological living substance in the animal experiment provide a platform to profoundly understand the mechanisms of damage and the pathogenesis of frostbite during low temperature exposure. The cryosurgical response of parenchymal tissue, i.e. ultrastructural cellular changes in parenchymal organs (liver and pancreas tissue), were investigated. This gives rise to a new concept concerning the technical requirements of cryosurgical equipment to perform modern cryosurgical operations, especially in oncology.
• The findings of the investigations allow to clearly define the clinical implication for the main technical requirements to cryosurgical devices. The main technical parameter stipulating for the effective cryodestruction is the provision of a high freezing rate of the biological tissue followed by further deliberate thawing.
• Phenomenon “Anthill Provocation Stimulus -Phenomenon” (APS-Phenomenon). There are natural phenomena that can be characterized by their analogy with physiological and pathological processes in the human organism. An anthill that constitutes an autonomous balanced subsystem can be transformed immediately into a “dynamic chaos” by exogenous interventions. Small impacts can already turn a snowfield into an avalanche through exponential dynamics. I am using these images in order to demonstrate a dead end of surgical oncology resulting very frequently in fatal consequences and human tragedies.
  An external intervention (“operation”) in an anthill will cause a defect which opens the previous “balanced state” of the entire closed ant autonomy locally The “gate” being created constitutes an anomaly to the system. This results in the destabilization of the entire system. A state of chaos being created – in this case temporarily only – will give impulses for activities by ants. The confused ants will accelerate their motion dynamics not only within the present system space, but expand it outwards as well.
• For the first time, it has been suggested that cold surgery is the first surgical technique to use anti-angiogenesis, especially in the treatment of malignant diseases.
• Phenomenon „Cryosurgical Avascular Tumor“ (CAT-Phenomenon). For the first time, the research results show that when the cryosurgical freeze-thaw cycle is finished and the cryozones with the ice crater in the middle, and the ice margin with the line of demarcation are thawed, the healthy liver parenchyma has taken on the colour of the dye. This occurs after cryosurgical application on the multiple liver metastases, but the cryoextirpated liver metastases have not been dyed, the cryoextirpated liver metastases are not dyed as well. Only the healthy hepatic parenchyma is sensitive to colour, but large liver metastases with the post-cryosurgical zone are not sensitive to colour. The absence of dye indicates a post-cryosurgical avascular tumor area.
• For the first time, summarized a long-term follow-up clinical experience with cryosurgery for treatment of liver metastases. The data of this 10-year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in the treatment of resectable and non-resectable liver metastases.
• The new concepts, discoveries, inventions and development of the unique high-tech and innovative cryogenic technology: instruments and devices are introduced in 51 National, European and International Patents (1984 - at present).
• Korpan’s and his Teams own investigations in modern cryoscience and cryomedicine in the last 30 years due to the development and performance of new about 2.600 unique modern curative and palliative cryosurgical operations that have been established the modern cryomedicine and cryoscience world-widely and will doubtlessly contribute to an upsurge in the use of this scientific and medical branch in the near future.
• Numerous workshops on modern cryoscience, cryomedicine, cryosurgery, and cryotechnology have been performed by Prof. Dr. Korpan together with his Teams at the several medical institutions world-widely (Austria, Germany, Hungary, Poland, Ukraine, Russia, Jordan, Iraq, Vietnam, etc.)
• Korpan’s and his Teams novel and fundamental contributions have been and will be achieved for world-wide cryoscience and cryomedicne, i.e., modern cryosurgery and cryotechnology on the national, European and international levels for the humanity in the 20th and the 21st centuries.

Main References

1. Korpan NN. Хирургическая тактика при непроходимости кишечника, обусловленной опухолевым процессом толстой кишки. Киев, 1981 (in Russian). [SurgicalStrategyinPatientswithTumorIleus, 1981].
2. Korpan NN. Криохирургия опухолей печени и поджелудочной железы. Харьков, 1984 (in Russian). [CryosurgeryforLiverandPancreas Tumor].
3. Korpan NN. Cryomethods in the General Surgery, 1984 (in Russian).
4. Korpan NN. External Hypothermia and Cryosurgery in the Treatment of Acute Pancreatitis, 1984 (in Russian).
5. Korpan NN. Низкие температуры в медицине. Киев, 1988 (in Russian). [Low Temperatures in Medicine].
6. Korpan NN. Гипотермия в неотложной брюшной хирургии. Киев, 1988 (inRussian). [Hypothermia in the urgent abdominal surgery].
7. Korpan NN. Cryosurgery of Liver Metastases from Colorectal Cancer: Long-Term Follow-Up. Pre and Post Course Symposium. Colorectal Disease in 1996: An International Exchange of Medical and Surgical Concepts. February 5-23, Cleveland Clinic Florida, Florida, USA. 1996:21-23.
8. Korpan NN. Hepatic Cryosurgery for Liver Metastases. Long-Term Follow-Up. AnnSurg 1997; 225:193-201.
9. Korpan NN, ed. Atlas of Cryosurgery. Vienna: Springer, New York, Vienna, Sydney, Tokyo, Munich, 2001; 525p.
10. Korpan NN, ed. Basics of Cryosurgery. Vienna: Springer, New York, Vienna, Sydney, Tokyo, Munich, 2001; 325p.
11. Korpan NN. The ’Lunar Eclipse’ Phenomena in Living Nature. Low Temp Med, 2006; 32(4):72-77.
12. Korpan NN. A History of Cryosurgery: Its Development and Future. J Am Coll Surg 2007; 204:314-324.
13. Korpan NN. Cryosurgery: Ultrastructural Changes in Pancreas Tissue after Low Temperature Exposure. Technol Cancer Res Treat 2007; 6:59-67.
14. Korpan NN. Cryosurgery: Early Ultrastructural Changes in Liver Tissue in vivo. J Surg Res 2009; 1:54-65.
15. Korpan NN. Cryoscience and Cryomedicine: Deciphering of the Effect of Deep Low Temperatures on Living Matter. Low Temp Med 2009; 35(3):65-74.