Organ Preservation Research Articles

Cascading renal injury after brain death: Unveiling glycocalyx alteration and the potential protective role of tacrolimus.

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain death-induced renal injury. This study aimed to investigate changes associated with brain death-induced renal injury in a 4-month-old female porcine model. The experimental groups included brain death placebo-pretreated (BD; n = 9), brain death tacrolimus-pretreated using the clinical dose of 0.25mg/kg the day before surgery, followed by 0.05mg/kg/day 1hour before the procedure (BD + FK506; n = 8), and control (ctrl, n = 7) piglets, which did not undergo brain death induction. Furthermore, we aimed to assess the effect of FK506 on these renal alterations through graft preconditioning. We hypothesized that immunosuppressive properties of FK506 reduce tissue inflammation and preserve the glycocalyx. Our findings revealed a series of interconnected events triggered by BD, leading to a deterioration of renal function and increased proteinuria, increased apoptosis in the vessels, glomeruli and tubules, significant leukocyte infiltration into renal tissue, and degradation of the glycocalyx in comparison with ctrl group. Importantly, treatment with FK506 demonstrated significant efficacy in attenuating these adverse effects. FK506 helped reduce apoptosis, maintain glycocalyx integrity, regulate neutrophil infiltration, and mitigate renal injury following BD. This study offers new insights into the pathophysiology of BD-induced renal injury, emphasizing the potential of FK506 pretreatment as a promising therapeutic intervention for organ preservation, through maintaining endothelial function with the additional benefit of limiting the risk of rejection.

Revolutionizing deceased donor transplantation: How new approaches to machine perfusion broadens the horizon for organ donation

Solid organ transplantation is lifesaving for persons with end-stage organ disease. Thanks to advancements in organ preservation, surgeons are now able to successfully transplant organs that were previously considered high risk for poor graft function. Innovations in perfusion machine types, preservation solutions and additives to preservation solutions have significantly improved the ability to utilize organs previously thought unusable.Newer organ preservation techniques are offering a promising outlook for extending graft longevity and improving transplant outcomes. This review explores the impact of deceased donor type on graft quality and highlights emerging strategies designed to improve the function and viability of deceased donor organs.

Machine Perfusion of Donor Hearts – The Recovery and Transplantation of Previously Unrecoverable Hearts

Heart transplantation remains the gold standard treatment for end-stage heart failure. With an increasing population and improving medical therapy there is an increasing number of patients who would benefit from heart transplantation but are unable to receive one due to a shortage of suitable donor organs. This ongoing need, and significant limitations with traditional cold static storage (CSS), have driven the development of machine perfusion technology that have expanded the donor pool. Machine perfusion is divided into hypothermic and normothermic, with both technologies perfusing the heart with oxygenated solution to reduce the degree of ischaemia-reperfusion injury that occurs. Both technologies have allowed for the safe retrieval and transplantation of hearts with prolonged ischaemic times or following donation after circulatory determination of death and have significantly increased the potential donor pool and number of transplants able to be safely performed. The aim of this review is to summarise the current options available to clinicians for donor heart organ preservation, with a focus on how the development of machine perfusion technology has allowed for the recovery of hearts previously considered unrecoverable using CSS.

A 25-year scoping review of the organ donation system in Malaysia: past, present, and future.

Organ donation and transplantation are integral components of modern medicine. This scoping review thoroughly explores the historical evolution, current status, and future prospects of organ donation and transplantation in Malaysia. Historically, Malaysia faced significant challenges in establishing a robust organ transplantation system, with various factors hindering organ donation efforts. Currently, Malaysia continues to struggle with stagnant donation rates despite collaborative efforts from various sectors. There is an urgent need to amend the 50-year-old Human Tissue Act to strengthen the legal framework for organ donation and address ethical concerns. Looking to the future, Malaysia could adopt a soft opt-out system and prioritize advancements in organ preservation techniques by exploring new sources of organs through the donation after circulatory death program. Continued efforts are necessary to enhance education programs for professionals and the public, dispelling myths about organ donation and effectively educating on the concepts of brain death. Malaysia strives to create a more accessible future for organ transplantation, aligning with the Sustainable Development Goals to reduce the burden of organ failure and improve the population's health and well-being.

Organic acid preservation of cereal grains improves grain quality, growth performance, and intestinal health of post-weaned pigs

This study investigated the effect of preserving wheat and barley grains with an organic acid liquid surfactant mould inhibitor compared to conventional artificial drying and assessed its effects on the health and performance of pigs post-weaning (PW). A 2 × 2 factorial arrangement was conducted to investigate the interaction between grain preservation method (dried vs. preserved) and zinc oxide (ZnO) inclusion (yes vs. no) on growth performance, diarrhoea scores and incidence, and total tract nutrient digestibility. One hundred and ninety-two pigs (3 pigs/pen; 16 replicates/treatment) were assigned to one of four experimental diets for 35 days: (1) dried grain diet, (2) preserved grain diet, (3) dried grain diet with ZnO and (4) preserved grain diet with ZnO. Diets were formulated to contain similar levels of net energy and standardised ileal digestible lysine. On day 35 PW, 24 pigs (12 replicates/treatment) from the non-ZnO supplemented groups were euthanised and digesta was collected for coefficient of apparent ileal digestibility (CAID), gut microbial population and volatile fatty acid analysis. Stomach tissue was also collected for gene expression analysis, as well as small intestine samples for gut morphology. Notable improvements in grain quality were observed in the preserved grain, including a reduction in grain pH, mould presence, and contamination by mycotoxins, specifically deoxynivalenol in wheat and barley, and ochratoxin A and HT-2 toxin in barley. The preserved grain diet improved average daily gain (ADG; P < 0.01) and body weight (BW; P < 0.01) compared to the dried grain diet. The incorporation of ZnO increased average daily feed intake (ADFI; P < 0.01) and BW (P < 0.05) in the dried grain diet, however, ZnO did not affect ADFI (P > 0.05), and reduced ADG and BW in the preserved grain diet (P < 0.05). Pigs offered the preserved grain diet had reduced faecal scores and diarrhoea incidence compared to those offered the dried grain diet (P < 0.05). Supplementation of ZnO reduced faecal scores and diarrhoea incidence compared to non-supplemented pigs (P < 0.001). On day 35 PW, the preserved grain diet had improved CAID of nitrogen and gross energy (P < 0.05), lower levels of colonic branched-chain volatile fatty acids (P < 0.05), and beneficial shifts in gut microbial populations. Specifically, there was a reduction in ileal Streptococcus (P < 0.001) and an increased abundance of colonic Faecalibacterium (P < 0.05). In conclusion, organic acid preservation improved grain quality, benefiting post-weaned pigs through improved nutrient digestibility and gut health, thus enhancing overall growth performance PW.

Do counts of radiocarbon-dated archaeological sites reflect human population density? A preliminary empirical validation examining spatial variation across late Holocene California

AbstractResearchers increasingly rely on aggregations of radiocarbon dates from archaeological sites as proxies for past human populations. This approach has been critiqued on several grounds, including the assumptions that material is deposited, preserved, and sampled in proportion to past population size. However, various attempts to quantitatively assess the approach suggest there may be some validity in assuming date counts reflect relative population size. To add to this conversation, here we conduct a preliminary analysis coupling estimates of ethnographic population density with late Holocene radiocarbon dates across all counties in California. Results show that counts of late Holocene radiocarbon-dated archaeological sites increase significantly as a function of ethnographic population density. This trend is robust across varying sampling windows over the last 5000 BP. Though the majority of variation in dated-site counts remains unexplained by population density. Outliers reveal how departures from the central trend may be influenced by regional differences in research traditions, development-driven contract work, organic preservation, and landscape taphonomy. Overall, this exercise provides some support for the “dates-as-data” approach and offers insights into the conditions where the underlying assumptions may or may not hold.

Combined Organ Transplantation in Patients with Advanced Liver Disease.

Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future.

Extending the boundaries of organ preservation: hope for heart transplantation

Extending the boundaries of organ preservation: hope for heart transplantation

261 High rate of Dropping from follow-up hinders implementing rectal cancer organ preservation protocols

261 High rate of Dropping from follow-up hinders implementing rectal cancer organ preservation protocols

Feasibility of a tailored operative strategy from organ preservation to pelvic exenteration for cT4 rectal cancer depending on neoadjuvant response

PurposeImprovements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE).MethodsPatients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included. All patients were treated with curative intent. Surgical management was adapted to tumour response. Kaplan–Meier curves were generated to compare 3-year overall survival (3y-OS), local recurrence (3y-LR) and distant metastases (3y-DM) between different strategies.ResultsAmong 152 patients included, 13 (8%) underwent OP, 71 (47%) TME and 68 (45%) APR/PE. The median follow-up was 31.3 months. Patients undergoing OP had a lower tumour pretreatment (p < 0.001). Compared to patients with TME, those with APR/PE had a higher rate of ypT4 (p = 0.001) with a lower R0 rate (p = 0.044). The 3y-OS and 3y-DM were 78% and 15.1%, respectively, without significant differences. The 3y-LR was 6.6%, and patients with OP had a significantly worse 3y-local regrowth compared to 3y-LR in patients with TME and APR/PE (30.2% vs. 5.4% vs. 2%, p = 0.008).ConclusioncT4 tumours may be suitable for the full spectrum of rectal cancer management from organ preservation to pelvic exenteration depending on tumour response to neoadjuvant therapy. However, careful attention is required in OP as local regrowth in up to 30% of cases reinforces the need for sustained active surveillance in Watch&Wait programmes.

Investigating the potential of unconventional resources in the Midland Basin: A comprehensive chemostratigraphic analysis of a Cline Shale (Wolfcamp-D) core

Basinal mudrocks assigned to the Wolfcamp Group in the Midland Basin are prolific producers of oil and gas. Technological advancements in horizontal drilling and hydraulic fracturing have been successful in the exploitation of oil and gas from these tight mudrocks. However, many challenges remain unsolved in capturing their macroscale compositional variations to enhance recovery factors and delineate “sweet spots”. To gain improved insights into this fine-grained system, high resolution chemostratigraphic (XRF) data was integrated with mineralogical measurements (XRD), logs, thin sections, and TOC readings, as well as hierarchical cluster analysis to: 1) develop a sequence stratigraphic framework, and 2) reconstruct paleo-redox, as well as ancient water-mass, conditions within the Cline Shale (Wolfcamp-D) from a core in the Midland Basin.This study revealed the presence of three chemo-stratigraphically distinct depositional sequences in the Cline Shale, herein termed Lower, Middle, and Upper Cline from the base upwards. All three units exhibit distinct mineralogical and petrophysical characteristics, were correlated across the basin, and interpreted as third-order sequences. Superimposed onto the three interpreted third-order sequences within the Cline, are potential higher frequency (fourth-order) sequences. These fourth-order sequences typically consist of a lower interval, interpreted as lowstand deposits and an upper interval, which is interpreted as transgressive and highstand deposits. The lower interval is interpreted to be deposited during highly reducing conditions while the upper interval is interpreted to be deposited under suboxic conditions. The highest organic matter preservation is associated with the interpreted lowstand deposits, especially in the Upper Cline. Optimal landing zones (20 ft) are recognized in the upper zone of the Cline Shale based on their high resistivity, total organic richness, elevated siliceous content, and reduced percentage of clay minerals. These zones have been correlated with several nearby wells.The current study demonstrates the wealth of information that can be gained from a single core/well when properly investigated at high resolution with measurements on a cm-scale. The observed shifts in the chemistry of the sediments character and composition are distinct, with implications for sequence stratigraphic analysis, the reconstruction of ancient water-mass conditions, and the identification of “sweet spots” for hydrocarbon resources. The provided analysis lays a foundational basis for further studies in the region, serving as critical data input for expansive regional research efforts.

Outcomes associated with total neoadjuvant therapy with non-operative intent for rectal adenocarcinoma.

To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival. These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.

Antimicrobial activity, foaming properties, and interacting mechanism of rhamnolipids in presence of silk fibroin through spectroscopy, molecular docking, and microbiological experiments

As a type of biosurfactant, rhamnolipids (RLs) are multifunctional skin-care ingredients, and the molecular interaction of RLs with silk fibroin (SF) is a more complicated process than has long been believed. The interaction and functional properties of them, and their potential as fungicidal agents for agricultural products and as organic preservatives for cosmetics were assessed in this paper. The SF addition makes the RLs aggregation easier through the complexes formation, which decreases the applied concentration of surfactant. The results of spectroscopic analyses and molecular docking suggest that hydrogen bonding and van der Waals forces are significant contributed to the binding mechanism between the two substances. The addition of SF notably enhances the foaming capacity and stability of RLs. The certain antibacterial and antifungal properties of RLs are basically not affected by the SF addition, even the SF-RLS system demonstrates an unobvious synergistic inhibitory impact on Glomerella cingulate (GC). The results offer a theoretical framework for the utilization of RLs as natural fungicides and preservatives in presence of nutritional components, considering the properties of RLs as nontoxic, biodegradable, environmentally friendly, and good compatibility.

Sequence of Contact X-ray Brachytherapy (CXB) and External Beam Radiation (EBRT) in organ-preserving treatment for small rectal cancer

Background and purposeExternal Beam Radiotherapy (EBRT) followed by Contact X-ray Brachytherapy (CXB) and vice versa are viable alternatives to surgery for selected rectal cancer patients who have small tumours (≤3 cm). However, the optimal sequence of treatment needs to be established. We compared two approaches using Propensity Score (PS) matching and inverse probability treatment weighting (IPTW) analyses to investigate whether the sequence of treatment affected patient outcomes. Materials and methodsThis retrospective analysis (2008–2019) included patients with rectal adenocarcinoma (cT1-3,N0-1,M0, grade 1–2, size ≤ 3 cm) who received both EBRT and CXB, irrespective of treatment sequence. PS matching and IPTW were conducted to balance covariate standardised mean differences between groups. Oncological outcomes and rate of post-treatment rectal bleeding were assessed. ResultsFollowing PS matching and IPTW analyses from 251 eligible patients; 103 starting with EBRT (median follow-up: 37 [IQR:18–56] months) and 148 with CXB (median follow-up: 32 [IQR:16–54] months, a significant improvement in 3-year overall survival (77% vs 85%, p = 0.02, [HR:0.58 (95% CI:0.37–0.91)]) and a higher risk of post-treatment rectal bleeding (grade 1 (26%) and grade 2 (6%)) were found in patients who started with CXB (p = 0.08). No significant differences were observed in local regrowth (18% vs 12%, p = 0.47), distant relapse (10% vs 6%, p = 0.53), 3-year organ preservation rates (70% vs 75%, p = 0.20, [HR:0.66 (95% CI: 0.35–1.26)]), or disease-free survival (78% vs 82%, p = 0.17, [HR: 0.47 (95% CI: 0.16–1.38)]) ConclusionIn patients with rectal cancer (≤3 cm), commencing with CXB rather than EBRT, was associated with improved overall survival, but had a higher risk of G1/2 rectal bleeding. No statistically significant differences were observed in other oncological outcomes.

Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer

BackgroundRecent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes.MethodsIn this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org.DiscussionBuilding on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer.Trial registrationClinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Machine perfusion in transplantation surgery

The use of machine perfusion in solid organ transplantation has developed tremendously worldwide in recent years. Although the number of randomized controlled trials in the field of organ preservation is still limited, machine perfusion has been shown to be superior to static cold storage of donor organs. Various devices for clinical use with hypothermia or normothermia are already available for most organs. Whether and which perfusion strategy is superior to the others is the subject of current clinical research. This also applies to the further evaluation of possible synergistic effects in the sequential use of the various protocols. The common goal of all dynamic perfusion technologies is to optimize organ preservation between removal and transplantation. By testing the quality of marginal donor organs prior to transplantation, it should also be possible to use these organs without exposing the patient to increased risk. This can lead to a significant expansion of the donor pool. This is particularly important in Germany, where there is an ongoing shortage of organs and restrictive legislation regarding the expansion of the donor pool. Furthermore, the perfusion technology offers the possibility to serve as a platform for other ex situ and in situ therapies on isolated organs. In addition to the conditioning of pre-damaged organs for transplantation, this could lead to further applications in the context of targeted organ therapies and also to improved transplant logistics in the future.

‘Folfirinox’ chemotherapy combined with contact x-ray brachytherapy 50 kVp and ‘CAP50’ chemoradiotherapy aiming at organ preservation for selected intermediate distal-middle cT2-T3 rectal cancers: A feasibility study

PurposeThe standard treatment of T2–T3 rectal adenocarcinoma is radical proctectomy by total mesorectal excision often combined with some neoadjuvant treatment. To reduce morbidity of this surgery, organ preservation strategy using various combination of radiotherapy, chemotherapy and local excision is gaining interest. Some randomized trials have proven the feasibility of such approaches. The OPERA trial demonstrated, for T2 T3<5cm diameter low-middle rectum, that a contact X-ray brachytherapy boost of 90Gy in three fractions over 4 weeks was able to achieve a planned organ preservation in 81% of patients at 3years with 97% success for tumour smaller than 3cm treated with contact X-ray brachytherapy boost first. To try to expand organ preservation to larger tumours we set up a feasibility trial in T2–T3 tumours using total neoadjuvant treatment and a contact X-ray brachytherapy boost. Material and methodThe trial was approved by the institutional review board of Nice. Inclusion criteria were operable patients, 75years or less, adenocarcinoma of the low-middle rectum staged T2c-T3N0 larger than 3.5cm and less than 6cm in diameter or T2-T3N1 less than 6cm in diameter. Treatment started in all cases with neoadjuvant chemotherapy associating 5-fluoro-uracile, irinotecan and oxaliplatin (‘folfirinox’ regimen, four to six cycles). In case of good tumour response after four cycles, a contact X-ray brachytherapy boost (delivering 90Gy in three fractions) was given followed by chemoradiotherapy (external beam radiotherapy delivering 50Gy, with concurrent capecitabine). After six cycles if only a partial response (tumour still larger than 3cm) was seen, chemoradiotherapy was given and contact X-ray brachytherapy boost was delivered after that. At the end of this total neoadjuvant treatment a watch and wait strategy was decided in case of clinical complete response or radical proctectomy by total mesorectal excision for partial response. ResultsBetween July 2019 and October 2022, 14 patients were included; median age was 66years (range: 51–77years), there were nine male and five female, two T2 N1 tumours, seven T3N0, and five T3N1, all were M0. Median tumour diameter was 40mm (range: 11–50mm); three tumours had a circumferential extension greater than 50%. Seven patients received four folfirinox cycles and seven had six cycles. Contact X-ray brachytherapy boost was given during folfirinox chemotherapy before chemoradiotherapy in 11 patients (and after in three). The tolerance was good, with no grade 4–5 toxicity. The main grade 3 early toxicity was in relation with the folfirinox regimen. A clinical complete response was seen in 12 patients at the end of the total neoadjuvant treatment (85%). All these patients are alive and have preserved their rectum with a mean follow-up time of 17.8months (range: 6–48months) and a good bowel function (low anterior rectal resection syndrome score below 30). The main contact X-ray brachytherapy boost toxicity was radiation ulceration in three patients that usually healed within 6 months, sometimes necessitating hyperbaric oxygen. ConclusionThe preliminary results of this feasibility study show that early tolerance of these intensive total neoadjuvant treatment is compatible with an acceptable toxicity. The high rate of organ preservation in this intermediate group of T2–T3 tumours is encouraging and is a good argument to start the next randomized TRESOR trial that will aim at achieving a 65% of 3-year survival with organ preservation in this intermediate tumour group.

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report

BackgroundSurgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer.Case presentationWe report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings.ConclusionA total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Investigating the stability of aromatic carboxylic acids in hydrated magnesium sulfate under UV irradiation to assist detection of organics on Mars

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument onboard the Mars 2020 Perseverance rover detected so far some of the most intense fluorescence signals in association with sulfates analyzing abraded patches of rocks at Jezero crater, Mars. To assess the plausibility of an organic origin of these signals, it is key to understand if organics can survive exposure to ambient Martian UV after exposure by the Perseverance abrasion tool and prior to analysis by SHERLOC. In this work, we investigated the stability of organo-sulfate assemblages under Martian-like UV irradiation and we observed that the spectroscopic features of phthalic and mellitic acid embedded into hydrated magnesium sulfate do not change for UV exposures corresponding to at least 48 Martian sols and, thus, should still be detectable in fluorescence when the SHERLOC analysis takes place, thanks to the photoprotective properties of magnesium sulfate. In addition, different photoproduct bands diagnostic of the parent carboxylic acid molecules could be observed. The photoprotective behavior of hydrated magnesium sulfate corroborates the hypothesis that sulfates might have played a key role in the preservation of organics on Mars, and that the fluorescence signals detected by SHERLOC in association with sulfates could potentially arise from organic compounds.