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organ and function preservation in gastrointestinal cancer: Current and future perspectives on endoscopic ablation

World Journal of Gastrointestinal Endoscopy 2024年第6期16卷 282-291页

作者： Youssef Yousry Soliman Megan Soliman Shravani Reddy James Lin Toufic Kachaamy Department of Gastroenterology City of Hope PhoenixGoodyearAZ 85338United States Department of Medicine Medical ConsultingGoodyearAZ 85395United States Department of Gastroenterology University of California IrvineIrvineCA 92697United States Department of Gastroenterology City of Hope National Medical CenterDuarteCA 91010United States

The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative *** treatment costs amount to billions of dollars annually,combined with the risks and comorbidities associated with invasive *** highlights the importance of less invasive alternatives with organ preservation being a central aspect of the treatment *** current standard of care typically involves neoadjuvant systemic therapy followed by surgical *** is a growing interest in organ preservation approaches by way of minimizing extensive surgical *** ablation has proven to be useful in precursor lesions,as well as in palliative cases of unrese-ctable *** recently,there has been an increase in reports on the utility of adjunct endoscopic ablative techniques for downstaging disease as well as contributing to non-surgical complete clinical *** expansive field within endoscopic oncology holds great potential for advancing patient *** addressing challenges,fostering collaboration,and embracing technological advancements,the gastrointestinal cancer treatment paradigm can shift towards a more sustainable and patient-centric future emphasizing organ and function *** editorial examines the evolving landscape of endoscopic ablation strategies,emphasizing their potential to improve patient *** briefly review current applications of endoscopic ablation in the esophagus,stomach,duodenum,pancreas,bile ducts,and colon.

关键词： Gastrointestinal cancer Endoscopic ablation organ preservation Complete clinical response Neoadjuvant therapy Endoscopic oncology Palliative treatment

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Addition of ulinastatin to preservation solution promotes protection against ischemia-reperfusion injury in rabbit lung

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Chinese Medical Journal 2011年第14期124卷 2179-2183页

作者： XU Ming WEN Xiao-hong CHEN Shu-ping AN Xiao-xia XU He-yun Department of Anesthesiology First Affiliated Hospital Zhejiang University School of Medicine HangzhouZhejiang 310003 China Department of Anesthesiology Hangzhou First People's HospitalHangzhou Zhejiang 310006 China Department of Cardiothoracic Surgery First Affiliated Hospital Zhejiang University School of Medicine HangzhouZhejiang 310003 China

Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution *** Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were *** The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two *** This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.

关键词： ischemia reperfusion injury organ preservation lung LPDG solution ulinastatin urinary trypsin inhibitor rabbits

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A study on continuous low-flow perfusion with low-potassium dextran for donor isolated lung preservation

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Chinese Medical Journal 1998年第1期111卷 49-51页

作者：邱罕凡廖崇先陈道中 Department of Cardiovascular Surgery Union Hospital Fujian Medical University Fuzhou 350001 China

OBJECTIVE: To test the validity of continuous low-flow perfusion with low-potassium dextran (LPD) to preserve rabbit lung. METHODS: Isolated rabbit lungs were preserved for eight hours either in Ringer's solution by simple storage (Group I) or in continuous low-flow perfusion with LPD (Group II). After preservation, lung functions were assessed to compare these two methods. RESULTS: The water gain in Group I was higher than that in Group II. During reperfusion, the functional test values for the immersed lungs were lower than those for the perfused lungs. The lipid peroxidation product (MDA) was significantly decreased in perfused lungs during reperfusion. CONCLUSIONS: Low-flow perfusion with LPD is better than immersion for the lung preservation.

关键词： Dextrans Lung organ preservation Solutions Potassium Animals Comparative Study In Vitro Male organ preservation Perfusion Rabbits

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Zinc is a potent heat shock protein inducer during liver cold preservation in rats

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Chinese Medical Journal 2002年第12期115卷 1777-1779,144-145页

作者：程颖刘永锋梁健中国医科大学第一临床医院器官移植科沈阳110001

OBJECTIVE: A simple liver cold preservation model was established to study the synthesis of heat shock protein 70 (HSP70) induced by zinc (ZnSO(4), i.p.) and its protection during liver cold preservation in rat. METHODS: Male Wistar rats were divided into 5 groups (n = 6). In control group rat received no pretreatment; in Zn-1 group, Zn-2 group, and Zn-3 group rats were pretreated with zinc sulfate at a dose of 5 mg/kg, 10 mg/kg, 15 mg/kg respectively; and in H group rat received heat shock preconditioning (42.5 degrees C x 15 min). Livers were preserved in UW solution for 6, 12 and 24 h, respectively. HSP70 was analyzed by Western blot. Aspartate transaminase (AST) and lactate dehydrogenase (LDH) values of the perfusion solution and the histology of the liver were evaluated. RESULTS: HSP70 expression was markedly elevated after pretreatment with zinc and heat shock. AST and LDH values in the Zn-1, Zn-2 and H groups were significantly lower than those in the control group, respectively (P 0.05), whereas the AST and LDH values in the Zn-3 group were much higher than those in the control group. Histology results showed that liver injury in the Zn-1, Zn-2 and H groups were minimal, while it was severe in the Zn-3 group. CONCLUSIONS: Zn(2+) is a potent and feasible inducer of HSP expression and is able to protect liver from cold preservation injury. The proper inducing dosage of Zn(2+) ranged from 5 mg/kg to 10 mg/kg. The dosage of 15 mg/kg for Zn(2+) as a HSP inducer is not indicated for its severe toxicity to the liver.

关键词： organ preservation Animals Aspartate Aminotransferases Dose-Response Relationship, Drug HSP70 Heat-Shock Proteins L-Lactate Dehydrogenase Liver Male Rats Rats, Wistar Zinc

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Liver graft preservation:an overview

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Hepatobiliary & Pancreatic Diseases International 2007年第1期6卷 12-16页

作者： Mohamed El-Wahsh University Department of Surgery Al Zhraa University Hospital Cairo Egypt

BACKGROUND: The quality of liver graft and outcome of liver transplantation is affected by the length of ischemia time during the donor operation. The retrieved graft may have a serious damage during the time of stoppage of the circulation in the donor until revascularization in the recipient. It is very important to develop a suitable preservation fluid to minimise the damage caused by the ischemic period and to make the surgical procedure semi- elective. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1960-2006) on liver preservation solution, liver transplantation, kidney transplantation and other related subjects. RESULTS: Since 1960 until 2006 many preservation solutions have been introduced. Most of them are based on the effect of hypothermia to minimise the metabolic pathway in the liver graft. In the earlier studies electrolyte solutions were used to perfuse the liver through the portal vein. The first modification in preservation solution was done by Collins who was able to extend the kidney preservation time up to 30 hours. In recent years, the introduction of University of Wisconsin (UW) preservation solution has made a revolution in the field of organ preservation. The UW solution is based on lactobionate and raffinose as impermeants to suppress hypothermic-induced tissue swelling, replacing glucose and mannitol in Collin's solution and hypertonic citrate respectively. Recently a research group in Kyoto University works to produce a more reliable preservation solution. They investigated the importance of saccharides and electrolytes in lung preservation and developed their original ET-Kyoto solution. However, more studies are still needed to evaluate the new ET-Kyoto solution. CONCLUSIONS: The development of new preservation solutions represents a corner stone in the field of organtransplantation. In the future we might be able to extend the time of organ preservation from hours to days.

关键词： organ preservation liver transplantation preservation solution ischemic damage UW solution

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A modified CZ-1 preserving solution for organ transplantation： comparative study with UW preserving solution

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Chinese Medical Journal 2008年第10期121卷 904-909页

作者： ZHENG Jun-hua MIN Zhi-lian LI Yu-li ZHU You-hua YE Ting-jun LI Jian-qiu PAN Tie-wen DING Guo-shan WANG Meng-long Department of Urology Shanghai 10th People's Hospital Tongji University Shanghai 200072 China Department of Urology Changzheng Hospital Second Military Medical University Shanghai 200003 China Department of Pathology Changzheng Hospital Second Military Medical University Shanghai 200003 China Department of Cardiovascular Surgery Changzheng Hospital Second Military Medical University Shanghai 200003 China Department of General Surgery Changzheng Hospital Second Military Medical University Shanghai 200003 China

Background The University of Wisconsin colloid based preserving solution （UW solution） is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng organ Preserving Solution （CZ-1 solution） and compared it with UW solution. Methods A series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied. Results There was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors＇ testicles. In some aspects, such as preserving rabbits＇ hearts, rats＇ intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22-31 hours were transplanted successfully and the mean renal function recovery time was （3.83±1.68） days. Conclusions CZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.

关键词： organ preservation preserving solution hypothermic ischemia

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Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 596-602页

作者： Wenzel Schoening Veeravorn Ariyakhagorn Thomas Schubert Peter Olschewski Andreas Andreou Peter Neuhaus Johann Pratschke Gero Puhl Allgemein- Visceral- & TransplantationschirurgieCharite Campus Virchow Klinikum General and Vascular Surgery Bumrungrad International Hospital Department of Pathology University of Erlangen

BACKGROUND： organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.

关键词： experimental liver transplantation static cold storage organ preservation ischemia-reperfusion injury

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Advances in Cryopreservation of organs

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第2期36卷 153-161页

作者：刘迪潘峰 Department of Urology Union HospitalTongji Medical UniversityHuazhong University of Science and Technology

organ transplantation is an effective approach for the treatment of end-stage organ failures. Currently, the donor organs used for clinical transplantation are all preserved at above-zero temperatures. These preservation methods are well-established and simple but the storage time lasts for only 4–12 h. Some researchers tried to extend the organ storage time by improving protectant and HLA matching to raise the use of stored organs and prolong the long-term survival of organs. These efforts still fall short of the clinical demand for organ transplantation. Moreover, a great many organs were wasted due to limited storage time, HLA mismatch, patients＇ conditions or distance involved. Therefore, preserving organs for several weeks or even months and establishing organ Bank are the tough challenges and have become a shared goal of global scholars. This article reviews some issues involved in the cryopreservation of organs, such as use of cryoprotecting agents, freezing and thawing methods in the cryopreservation of hearts, kidneys and other organs.

关键词： cryopreservation organ preservation organ transplantation cryoprotectant vitrification antifreeze proteins

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Watch and wait approach in rectal cancer:Current controversies and future directions

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World Journal of Gastroenterology 2020年第29期26卷 4218-4239页

作者： Fernando López-Campos Margarita Martín-Martín Roberto Fornell-Pérez Juan Carlos García-Pérez Javier Die-Trill Raquel Fuentes-Mateos Sergio López-Durán JoséDomínguez-Rullán Reyes Ferreiro AlejandroRiquelme-Oliveira Asunción Hervás-Morón Felipe Couñago Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Radiology Hospital Universitario de BasurtoBilbao 48013VizcayaSpain Department of Surgery Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Medical Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Gastroenterology and Hepatology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Medical Oncology Hospital Infanta CristinaMadrid 28034Spain Department of Radiation Oncology Hospital Universitario QuirónsaludMadrid 28003Spain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Universidad Europea de Madrid(UEM) Madrid 28223Spain

According to the main international clinical guidelines,the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by ***,doubts have been raised about the appropriate definition of clinical complete response(cCR)after neoadjuvant therapy and the role of surgery in patients who achieve a *** resection is associated with significant morbidity and decreased quality of life(QoL),which is especially relevant given the favourable prognosis in this patient subset. Accordingly, therehas been a growing interest in alternative approaches with less morbidity,including the organ-preserving watch and wait strategy, in which surgery isomitted in patients who have achieved a cCR. These patients are managed with aspecific follow-up protocol to ensure adequate cancer control, including the earlyidentification of recurrent disease. However, there are several open questionsabout this strategy, including patient selection, the clinical and radiologicalcriteria to accurately determine cCR, the duration of neoadjuvant treatment, therole of dose intensification (chemotherapy and/or radiotherapy), optimal followupprotocols, and the future perspectives of this approach. In the present review,we summarize the available evidence on the watch and wait strategy in thisclinical scenario, including ongoing clinical trials, QoL in these patients, and thecontroversies surrounding this treatment approach.

关键词： Watch and wait Rectal cancer Clinical complete response organ preservation Dose intensification

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Therapeutics administered during ex vivo liver machine perfusion:An overview

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World Journal of Transplantation 2020年第1期10卷 1-I0001页

作者： Julianna E Buchwald Jing Xu Adel Bozorgzadeh Paulo N Martins Division of Transplantation Department of Surgery University of Massachusetts Medical School

Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and *** this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation *** various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of *** vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during *** use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science *** novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.

关键词： Therapeutics Liver transplantation Ex vivo machine perfusion Ischemia reperfusion injury organ preservation Extended criteria donors

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