Organ Preservation Research Articles

Transanal endoscopic microsurgery vs. radical surgery for mid-low rectal cancer in patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy.

e15616 Background: Following neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision surgery used to be the standard therapy for locally advanced rectal cancer (LARC). However, the radical surgery is associated with high complication rates and impairs patients' quality of life, especially for non-sphincter preservation procedures. For the past two decades, nCRT followed by organ preservation strategies like watch-and-wait (W&W) or local resection offers an alternative for patients being clinically evaluated with complete response or near complete response, however the oncological outcomes of these approaches require further exploration. Methods: We prospectively collected data on 80 patients with T3-4N0M0 or TanyN+M0 mid-low rectal cancer who achieved cCR or near-cCR after nCRT from May 2017 to September 2021 at 5 tertiary centers in China. Patients were divided into the TEM group (group A) or the radical surgery group (group B). Clinicopathological features, operative outcomes, oncological and functional results were analyzed. Results: A total of 76 cases were analyzed, with 38 in each group. Baseline characteristics were comparable between the two groups. Postoperative histology revealed 22 ypT0Nx(57.9%), 5 ypT1Nx(13.2%), 10 ypT2Nx (26.3%), 1 ypT3Nx(2.6%) in group A, and 18 ypT0N0 (47.4%), 5 ypT1N0 (13.2%), 11 ypT2-3N0 (28.9%), 1 ypT0N1 (2.6%), 3 ypT2-3N1 (7.9%) in group B. After a median follow-up of 61 months, 2 patients (5.26%) in group A experienced local recurrence, while none in group B. 8 patients (21.05%) in group A developed distant metastases compared to 5 (13.16%) in group B. There was no statistically significant difference between two groups in 5-year disease-free survival(P = 0.320), or 5-year overall survival (P = 0.425). Patients in group A had significantly faster postoperative recovery and a superior quality of life evaluated by the Wexner and LARS scores compared to group B. Conclusions: For cCR and near-cCR LARC patients after nCRT, organ preservation with TEM may serve as a staging method to evaluate local tumor persisrence. And it provides an alternative therapy for carefully selected patients who have needs to preserve sphincteric function or can’t tolerate radical resection, without significantly compensate long-term oncological outcomes. This strategy could relatively safely enable sphincteric function preservation for these patients with faster postoperative recovery and better quality of life. Clinical trial information: NCT03042000 .

Long term outcome of patients with rectal cancer with complete clinical response or near complete clinical response after neoadjuvant therapy: A multicenter registry study by Chinese Watch and Wait Database.

e15597 Background: To report the long-term outcomes of Chinese rectal cancer patients after Watch and Wait (W&W) following neoadjuvant therapy(NAT). Methods: Collecting real-world multicenter retrospective data, including the Chinese W&W Database group (CWWD) and data from centers that initiated this work earlier in China. Patients with a follow-up time of no less than 2 years were included. Analyzing and reporting on their oncological outcomes and comparing differences between cCR and near-cCR groups. Results: The study included 318 rectal cancer patients from 8 institutions who received NAT and underwent W&W. Among them, 291 initially achieved cCR, and 27 had near-cCR. The median follow-up time was 48.4 months (10.2-110.3 months). The 5-year OS and CSS were 92.4% (95% CI 86.8-95.7%) and 96.6% (95% CI 92.2-98.5%), respectively. The 5-year OP-DFS(organ preservation adapted DFS) was 86.6% (95% CI 81.0-90.7%), and the 5-year OPR was 85.3% (95% CI 80.3-89.1%). The overall 5-year local regrowth rate and distant metastasis rate were 18.5% (95% CI 14.9-20.8%) and 8.2% (95% CI 5.4-12.5%), respectively. The 5-year local regrowth rate in the near-cCR group was higher than in the cCR group (41.6% vs. 16.4%, p<0.01), with a lower OPR rate (69.2 vs. 88.0%, p<0.001). However, there were no significant differences in OS, CSS, and OP-DFS between the two groups. 91% of local regrowths occurred within the intestinal lumen, 7.2% (4/56) occurred simultaneously in the intestinal lumen and mesentery, and 1.8% (1/56) occurred only in the mesentery. 82.1% of local regrowths occurred within 2 years, 91.0% occurred within 3 years, with a median regrowth time of 11.7 months (2.5-66.6 months). Among cases with local regrowth beyond 2 years, 30% (3/10) had mesenteric regrowth. The salvage success rate after local regrowth (conversion to disease-free status after salvage surgery) was 82.1% (46/56). 60.8% of distant metastases occurred within 2 years, 73.9% occurred within 3 years. Common sites included lung metastasis (65.2%), liver metastasis (34.8%), and bone metastasis (30.4%), with 26% involving multiple organs. 83.3% (5/6) of liver metastases occurred within 2 years, while lung and bone metastases spread out over 5 years follow-up. Among patients with local regrowth, 16.0% (9/56) developed distant metastases. The salvage success rates for local regrowth and distant metastasis were 82.1% (46/56) and 12.5% (3/23), respectively. Conclusions: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local regrowth and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local regrowth. It emphasizes the importance of close follow-up and timely intervention during the W&W process.

An economic analysis of low-energy contact x-ray brachytherapy for treatment of rectal cancer.

e15622 Background: Health Technology Wales sought to evaluate the clinical and cost-effectiveness of contact x-ray brachytherapy (CXB) in conjunction with external-beam radiotherapy (EBRT), compared to EBRT alone for early-stage (T2–3b, N0–1, M0) rectal cancer in a surgically fit population. Methods: An economic analysis was performed using a decision analytical, state transition model. Analysis was performed from a third-party payer perspective over a life-time horizon. The model was populated using data from the Organ Preservation in Early Rectal Adenocarcinoma (OPERA) trial. Results: . CXB was estimated to provide 0.2 quality-adjusted life years (QALYs) per patient at an additional cost of $1118 per person. CXB was cost-effective compared with external beam boost at a cost of $5623 per QALY gained. These findings did not change in deterministic sensitivity analysis and CXB was cost-effective in over 90% of probabilistic sensitivity analyses. Conclusions: CXB is likely to be cost-effective with a high degree of certainty in this patient population.

251P Phase II study of organ preservation (OP) using neoadjuvant chemotherapy (Ctx) and local excision (LE) in node-negative (NN) low rectal cancer (RC)

251P Phase II study of organ preservation (OP) using neoadjuvant chemotherapy (Ctx) and local excision (LE) in node-negative (NN) low rectal cancer (RC)

Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).

Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).

Contact x-ray brachytherapy for the treatment of rectal cancer: A systematic review and meta-analysis.

e15628 Background: Rectal cancer is a highly prevalent disease, particularly among the elderly and frail populations. While surgical resection has traditionally been the primary management approach, it carries inherent risks, including operative mortality, morbidity, and poor long-term functional outcomes. These risks are particularly pronounced in older, co-morbid individuals. Evidence presented in the 2023 phase III OPERA randomised trial suggests that Contact X-ray Brachytherapy (CXB) is a viable organ-preserving alternative to radical surgery. We conducted a systematic review and meta-analysis to assess the clinical effectiveness of CXB in the treatment of rectal cancer. Methods: This systematic review was prospectively registered (CRD42021284969) and reported in accordance with PRISMA guidelines. PubMed, EMBASE, SCOPUS and Cochrane CENTRAL Libraries were interrogated using the search terms “Rectal cancer”, “Contact Brachytherapy”, and synonym terms. Literature search and data extraction were conducted by two reviewers, with recourse to a senior author for resolution of conflicts. Clinical complete response (cCR) was the primary outcome. Secondary outcomes include local regrowth, regional recurrence, salvage surgery rates, long-term disease control post-salvage surgery and survival outcomes. Proportional meta-analyses were conducted and presented as forest plots with summary proportions and 95% confidence intervals. The Higgins I2 statistic was used to assess for heterogeneity. The random effects model was employed in studies reporting substantial heterogeneity (I2> 50%). Results: The literature search identified 973 studies, of which 48 studies encompassing 5,447 patients were included in the meta-analysis. Pooled estimates of outcomes were as follows: cCR rate = 80% (95% CI 76-88%), local regrowth = 15% (95% CI 12-18%), regional failure rate = 3% (95% CI 2-4%), salvage surgery rate = 14% (95% CI 11-18%), long-term disease control post-salvage surgery rate = 88% (95% CI 78-96%) and organ preservation 82% (95% CI 75-88%). A subgroup analysis was conducted and stratified by concomitant therapy (CXB alone, CXB & EBRT, CXB & EBCRT). CXB, in conjunction with EBCRT, leads to a statistically significant reduction in both local regrowth and regional failure. The local regrowth rates were 16% (95% CI 11-21%), 17% (95% CI 11-23%), and 10% (95% CI 8-13%) respectively, with a p-value of 0.05. The regional failure rates were 4% (95% CI 2-8%), 4% (95% CI 2-5%), and 1% (95% CI 0-2%), p = 0.02. Conclusions: CXB, combined with EBCRT, in the appropriately selected patient can achieve long-term disease control whilst avoiding major surgery. Salvage surgery is a viable option for patients who experience disease regrowth, with excellent long-term disease control. CXB may be considered a safe alternative to surgery in the appropriately selected patient.

Neoadjuvant pembrolizumab/nab-paclitaxel/cisplatin in patients with locally advanced head and neck squamous cell carcinoma: A single-arm phase II study.

e18043 Background: Despite multimodality standard therapy, patients with locally advanced head and neck squamous cell carcinoma are at high risk of recurrence and distant metastasis. The safety and efficacy of immunotherapy (pembrolizumab) has been reported in patients with recurrent/metastatic HNSCC. We hypothesized that neoadjuvant chemo-immunotherapy has a positive effect on decreasing distant metastasis, preserving organ function and extending survival time. Methods: In this prospective, non-randomized, single-arm phase II clinical trial, patients meeting the inclusion criteria were treated neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 260 mg/m2 Nab-paclitaxel per 3 weeks for 2 cycles.Patients will undergo the first radiologic imaging assessment after neoadjuvant therapy. After multi-disciplinary team discussion, patients with Partial Response (PR) but the maximum diameter of tumor > 3cm or stable disease (SD) or progressive disease (PD) receive surgery and standard adjuvant therapy. On the other hand, patients with PR and maximum tumor diameter ≤ 3cm or Complete Response (CR) receive definitive CRT. Evaluation was performed 3 months after definitive CRT and patients with high-risk factors need maintenance treatment. Primary outcomes are objective response rate (ORR), safety, rate of organ preservation. Results: A total of 31 patients were enrolled with a median follow-up of 6.6 months (1.4-20.2m). The baseline characteristics were shown in the table. Among 31 LA HNSCC patients with 2 cycles of neoadjuvant therapy, ORR was 64.52% (20/31) and DCR was 100%. 10patients underwent surgery with R0 resection, and 17 patients received definitive CRT,4 patients refuse surgery or CRT and out of trial. There was 20/31 (64.5%) organ function preservation. Among those with definitive CRT, no recurrence or distant metastasis occurred. In this trial, there's no Grade≥3 treatment-related adverse events. One patient died due to cardiacarrest and the correlation with study cannot be evaluated. Conclusions: Neoadjuvant chemo-immunotherapy contributed to good ORR and organ function preservation, and generally tolerated in LA HNSCC. This study is ongoing. And we look forward to demonstrating that neoadjuvant immunochemotherapy is expected to improve long-term survival of LA-HNSCC. Clinical trial information: NCT05272696 . [Table: see text]

Preliminary efficacy and safety of total neoadjuvant therapy combined with PD-L1 blockade in pMMR/MSS locally advanced rectal cancer (ESTIMATE): A prospective, single-arm, phase II trial.

e15602 Background: Patients with locally advanced rectal cancer (LARC) experience benefits from total neoadjuvant therapy (TNT). This study aims to explore the efficacy and safety of combining TNT with immunotherapy for pMMR/MSS LARC patients. Methods: ESTIMATE is a prospective, single-center, phase II study (ChiCTR2400079718) enrolling pMMR/MSS LARC patients with tumors located 10cm away from the anal margin. Treatment involved induction chemotherapy with immunotherapy ([mFOLFOX6, days 1-2 + Envafolimab 200mg, ih, day 1]; q2w; 2 cycles), long-course concurrent chemoradiotherapy (LCRT) with immunotherapy ([IMRT, 50Gy/25f, 2Gy + Cape 825mg/m2, bid]; 5w + Envafolimab 200mg, ih, day 1; q2w; 3 cycles), consolidation chemotherapy with immunotherapy ([mFOLFOX6 + Envafolimab; 2 cycles), and then total mesorectal excision (TME) 3 weeks later or watch and wait (W&W). The primary endpoint is the pathological complete response (pCR) rate. Results: Until Nov. 16th, 2023, 35 patients were enrolled, with 28 completing the TNT regimen. The efficacy analysis revealed that out of 28 patients, 12 (42.9%) achieved clinical complete response (cCR), with 7 individuals choosing the W&W strategy. 21 patients underwent TME, yielding 8 with a tumor regression grade (TRG) of 0, 7 with TRG of 1, and 6 with TRG of 2. The rates of pCR, major pathological response (MPR), and complete response (CR) were 38.1% (8/21), 71.4% (15/21), and 53.6% (15/28), respectively. 25 (89.3%) patients experienced treatment-related adverse events (AEs) of any grade. Non-hematological AEs included decreased appetite, fatigue, nausea, and vomiting, while hematological AEs mainly comprised thrombocytopenia, anemia, and leukopenia or neutrophilia. Grade III AEs were primarily leukopenia or neutrophilia (2/28, 7.1%). Additionally, circulating tumor DNA (ctDNA) levels were measured in 7 patients who chose the W&W strategy after achieving cCR. Of these, 6 tested negative for minimal residual disease (MRD), while 1 had a positive MRD result (ctDNA: 0.56 MTM/ml). As of Jan. 26th, 2024, with a median follow-up of 5 months (range: 3-6), no recurrence was observed in any of the patients. Conclusions: The TNT approach, integrating LCRT with mFOLFOX6 and PD-L1 blockade, demonstrated a favorable CR rate and acceptable tolerability, offering a potential avenue for organ preservation in low rectal cancer patients with pMMR/MSS. Long-term benefits need validation through further follow-up. Clinical trial information: ChiCTR2400079718. [Table: see text]

277TiP Total neoadjuvant therapy and organ preservation versus surgery for rectal cancer prospective, non-inferiority, randomized, controlled trial (STart)

277TiP Total neoadjuvant therapy and organ preservation versus surgery for rectal cancer prospective, non-inferiority, randomized, controlled trial (STart)

Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2 overexpression: Preliminary results of a prospective, single-arm, phase II study.

e16100 Background: A combination of HER2-targeted therapy, immunotherapy and chemotherapy is being explored in the perioperative treatment of gastric/gastric junction (GC/GEJ) adenocarcinoma.Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), demonstrated significant anti-tumor activity. Moreover, data suggest that the combination of RC48 with immunotherapy exhibits a synergistic effect. Therefore, we conducted the study to investigate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for locally advanced, resectable GC/GEJC with HER2 overexpression. Methods: In this prospective, phase II, single-arm study, we included patients with histologically confirmed, resectable gastric/gastric junction adenocarcinoma (GC/GEJ) staged as cT3-4aN1-3M0 according to the TNM 8th edition, and demonstrating HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment on a three-weekly basis (Q3W). Surgical resection was scheduled to occur 3-4 weeks following the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate; the secondary endpoints included the major pathological response (MPR) rate, clinical downgrading rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Sep 18, 2022 and Feb 2, 2024, a total of 23 patients were enrolled. Seven patients had not completed neoadjuvant treatment.Two patients refused surgery due to organ preservation. Two patients refused study therapy after 2 cycles of neoadjuvant treatment. 12 patients who experienced D2 resection, 6 (50%) achieved MPR, including 4 (33.3%) with pCR (ypT0N0M0).The R0 resection rate was 100%. Median DFS and OS have not been reached. The most common reported AEs (grade≥3) were decreased neutrophil count (10%), bowel obstruction (5%), ALT increased (5%) and AST increased (5%). There have been no treatment-related mortalities documented. Conclusions: The preliminary findings suggest that the neoadjuvant combination of RC48, camrelizumab and S-1 presents a promising and safe treatment option for locally advanced resectable GC/GEJ adenocarcinoma with HER2 overexpression. Clinical trial information: ChiCTR2300075446.

Infections Connected with Organ and Tissue Transplantation

Abstract Transplantology is a branch of medicine that is developing rapidly. Transplanted whole organs or segments of organs may be recovered from either living or deceased donors. New methods of preserving transplanted solid organs, including the kidney, liver, heart, lung, and pancreas, as well as tissues, such as the cornea and skin, are being developed. Preservation fluid, which is used to perfuse and store the donated organ or tissue, should reduce biological deterioration of organs and tissue, attenuate ischemia/reperfusion-induced cell/tissue injury, and protect against damage. Lowering the storage temperature of organs significantly reduces the risk of damage. Efforts are also made to shorten the time between collecting the organ or tissue from the donor and transplanting it in the recipient. However, during transplantation, the recipient may become infected, primarily with bacteria and fungi. Infections of organ recipients occur most often due to unhygienic organ collection, improper handling and transport, and inappropriate preservation conditions, especially contamination of preservation fluid. The literature on contamination of organ preservation fluid and infections in graft recipients is very diverse, both in terms of the isolated bacterial and fungal species and the number of incidents. A large percentage of contaminating microorganisms belong to the generally non-pathogenic skin microbiota, but there are also cases of multidrug-resistant bacteria. Besides, the transplanted organs themselves may pose a danger. They may contain latent microorganisms, mainly viruses and parasites, that could be activated in a patient who has been subjected to immunosuppression to reduce the risk of organ rejection.

A phase II trial of neoadjuvant docetaxel/5-FU/cisplatin in combination with prophylactic pegteograstim in unresectable, locally advanced nasal cavity/paranasal squamous cell carcinoma: KCSG HN18-07.

6020 Background: Squamous cell carcinoma (SCC) arising from paranasal sinus and nasal cavity (PNSNC) is often diagnosed at locally advanced stage. Neoadjuvant strategies have been explored to improve prognosis and facilitate organ preservation. The efficacy of triplet neoadjuvant chemotherapy (NAC) has not been established prospectively. We conducted a phase II trial of neoadjuvant docetaxel/5-FU/cisplatin (DFP) combined with prophylactic pegteograstim in unresectable, locally advanced PNSNC (KCT0003377). Methods: Eligible patients had unresectable SCC of PNSNC, were aged 19-75, had an ECOG performance status of 0/1, and demonstrated adequate organ function. Patients with distant metastasis were excluded. Criteria for unresectability included tumor or lymph node fixation, clinical T3/4 stage, or potential compromise of critical organ function (e.g., necessitating eyeball exenteration). NAC comprised three cycles of docetaxel (75mg/m2 on Day 1), cisplatin (75mg/m2 on Day 1, 60mg/m2 for those aged ≥65), and 5-FU (1,000mg/m2 on Days 1-4) administered every 3 weeks. Prophylactic pegteograstim (6mg) was administered on Day 6 or 7. The primary outcome was the overall response rate (ORR), with secondary outcomes including progression-free survival (PFS), the eyeball preservation rate at 24 months, and safety. The study required 28 patients to achieve a power of 80% (P0=0.45, P1=0.70, α-error=0.05, 10% dropout rate). Results: Between 2019 and 2023, 28 patients were screened, and 27 received at least one cycle of NAC. The median age was 58 years (range: 41-71), with 24 males. Seventeen had maxillary sinus origin, and ten had nasal cavity origin. Twenty-two patients had T4 disease, and six had N2 disease. The ORR was 64.3% (5 complete responses, 13 partial responses). Post-NAC treatments included surgery alone (n=2), concurrent chemoradiotherapy (CCRT) (n=15), surgery followed by CCRT (n=2), or radiotherapy (RT) (n=5). Procedures performed were total maxillectomy (n=4), partial maxillectomy (n=3), and endoscopic sinus surgery (n=2). With a median follow-up of 21.5 months (range: 0.1-53.0), the 2-year PFS and eyeball preservation rate were 64% and 100%, respectively. Fourteen patients experienced Grade ≥3 adverse events (AEs): hematologic (46.4%), non-hematologic (14.3%), with Grade 3/4 neutropenia (32.1%) and febrile neutropenia (14.3%). Dose reduction or delay occurred in 9 patients (33.3%). One patient died on Day 6 of cycle 1. Conclusions: DFP NAC demonstrated promising efficacy and an excellent eyeball preservation rate with manageable toxicity. DFP NAC with prophylactic pegteograstim, could be a reasonable option for patients with locally advanced SCC of the PNSNC. Follow-up is ongoing. Clinical trial information: KCT0003377 .

247P Radiotherapy (RT), atezolizumab (atezo) and bevacizumab (bev) to increase organ preservation in rectal cancer: The TARZAN study

247P Radiotherapy (RT), atezolizumab (atezo) and bevacizumab (bev) to increase organ preservation in rectal cancer: The TARZAN study

Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX).

Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX).

Total Neoadjuvant Therapy for Rectal Cancer: Which Regimens to Use?

Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.

Comparing advanced platforms for local excision of rectal lesions.

Transanal surgery facilitates organ preservation in select patients with benign and early malignant rectal lesions to avoid the functional consequences of radical surgery. The transanal endoscopic microsurgery (TEM) platform created a standard for local excision with lower margin positivity and recurrence rates than traditional transanal excision. The single-port robot (SP r) presents a promising alternative transanal platform. The goal of this study was to compare perioperative and pathologic outcomes of TEM and SP r for excision of rectal lesions. A review of consecutive patients who underwent local excision of rectal lesions at a tertiary referral center from 1/2001 to 5/2022 was performed. Cases were stratified into TEM or SP rTAMIS in a 1:1 propensity score-matched cohort, adjusting for all baseline characteristics. Clinical, tumor-specific, and perioperative outcomes were compared using χ2, and Mann-Whitney U-tests. The main outcomes were oncologic quality measures, complications, and operative time. Matching resulted 50 patients in each cohort. Groups had similar age, gender, body mass index, comorbidity, diagnosis, lesion characteristics, and neoadjuvant chemoradiation rates. There were no intraoperative complications in either cohort. Three SP rTAMIS cases were converted intraoperatively; there were no conversions in TEM. SP rTAMIS had significantly shorter operative times than TEM (mean 104 vs. 245, p = 0.027). The rates of positive distal margins (2% TEM, 0% SP rTAMIS) and piecemeal resection (4% TEM, 0% SP rTAMIS) were similar. SP rTAMIS had significantly lower postoperative morbidity rates than TEM (9% vs. 20%, p = 0.031). There was no mortality in either cohort. SP robotics provided high-quality outcomes similar to TEM for local excision of rectal lesions. SP robotics had faster operative time with comparable clinical and oncologic outcomes to TEM. These early data are promising for expanding use of SP robotic platforms.

Current treatment of pT1 rectal cancers in Denmark: Aretrospective national cohort study.

Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Rates of sedimentary organic carbon preservation in the Bering Sea and Chukchi Sea, and their response to climate change over the past 75 years

The Arctic Ocean is rapidly warming. In this paper, we document changes in the source, distribution, and accumulation rate of organic matter (OM) for three sediment cores in the Bering and Chukchi seas to investigate changes to the oceanic carbon cycle over the past ∼75 years. Analyses were undertaken using bulk properties, such as total organic carbon (OC), total nitrogen (TN), stable carbon isotope (δ13C), OC to TN molar ratio (C/N), and biomarkers (lignin phenols). The OC, TN, and lignin (Σ8, in mg (g sediment)−1) contents were found to be significantly related to the fraction of sand (Sand%) as a result of sediment sorting and/or different sediment sources. Using an end-member mixing model, we estimated marine OM accounted for ∼67% of all organic matter in all cores, being the dominant source. Moreover, terrestrial OM mainly originated from angiosperm non-woody tissue, while moss contribution was negligible. In the Bering Sea shelf, OC% has not changed over time, but there have been some extreme peaks around the 1960s–1970s and in 2005, which correspond to increased terrestrial input from North American rivers. In the southern core from the Chukchi Sea, the OC% showed an apparent decrease after 2000, accompanied by an increase in sand content, likely due to enhanced delivery of volcanic rocks by the Pacific Inflow from the Bering Sea. In contrast, in the northern core from the Chukchi Sea, the OC% showed a significant increasing trend, with some peaks occurring at the same time as in the Bering Sea core. The mean increase rate was compared to the increase in Siberian riverine discharge, which both could be caused by long-term climate changes. The results highlight the regional differences in the response of OC preservation to climate change and other controlling factors. Further studies with higher spatial resolution are required to better understand the preservation of OC in response to climate change.

Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis.

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

Reduction in pacemaker rates post-heart transplantation with use of organ preservation systems

Abstract Background Approximately 10% of heart transplant recipients require permanent pacemaker (PPM) implantation. (1) Prolonged graft ischaemic time may contribute to conduction system injury and PPM requirement. (2) Ex-vivo preservation of heart allografts at the time of organ retrieval, using either normothermic or hypothermic organ preservation systems (OPS), allows for the reduction of graft ischaemic time which can facilitate long-distance procurements and use of marginal donors including donation after circulatory death (DCD) donors. (3) Purpose We sought to determine if the use of organ preservation systems reduced PPM implantation in heart transplant recipients. Methods This was a single-centre retrospective study of 405 consecutive heart transplant recipients between July 2014 and March 2023. Baseline demographics, utilisation of organ preservation systems, donor ischaemic times, history of graft dysfunction, rejection and chronic allograft vasculopathy were obtained from the medical records. The primary outcome was PPM implantation. Results Of 405 heart transplants performed, an organ preservation system (OPS) was utilised in 118 (29.1%) patients. Normothermic OPS was used in 93/405 (23%) transplants, 90 of which were DCD transplants. Twenty-five of 405 (6.2%) transplants were performed using a hypothermic OPS to facilitate donation after brain death (DBD). The remaining 287 (70.9%) organs underwent cold ischaemic storage (CIS) from retrieval until transplant. Apart from male sex (81% in OPS group versus 69% in the CIS group), there were no significant differences in baseline demographics between the two groups (table 1). Two of 118 (1.7%) patients in the OPS group required PPM implantation, compared to 27/287 (9.4%) in the cold ischaemic storage group (Chi-Square 7.5, p = 0.006). Kaplan-Meier analysis (figure 1) demonstrates a significantly lower rate of PPM implantation in the OPS arm (Log Rank 6.975, p = 0.008). Of the 29 patients who required pacing, 12/29 (41.4%) had AV block and 17/29 (58.6%) had sinus node dysfunction. Thirteen of 29 patients (44.8%) required PPM implantation within 30 days of transplant. Six of 29 patients (20.7%) were pacing dependent at last follow up. Conclusion Heart transplants performed utilising an organ preservation system were associated with lower PPM rates.Table 1.Figure 1.