Recurrence Of Primary Disease Research Articles

Evaluation of the safety and effectiveness of robot-assisted neck dissections.

Robot-assisted neck dissection (RAND) for the management of the regional lymphatic basin offers the potential for improved cosmesis and reduced lymphedema. While RAND has been previously described, functional outcome and oncologic control rates need further elucidation. A retrospective, matched cohort study of neck dissections completed at UPMC from 2017 to 2021 was conducted. RAND was identified and matched to open neck dissections (open) in a 1:2 ratio. Matching characteristics included primary cancer site, pre-operative clinical N-stage, age at time of surgery, HPV status, and previous chemoradiation treatment (salvage vs. nonsalvage procedure). Additional information was collected on patient demographics, surgery characteristics, and outcomes. Comparisons were made using t-test, chi-square test, Fisher's exact test, and Kaplan-Meier Wilcoxon (KMW) test with p < 0.05 indicating significance. Overall, RAND and open groups had similar distributions of age, gender, BMI, primary site of cancer, HPV status, clinical N-stage, clinical T-stage, known neck disease prior to procedure, prior chemoradiation therapy, and level(s) of neck dissection. Surgically, RAND procedures yielded less drainage on average (124 mL in RAND vs. 220 mL in open approaches; p = 0.01). There was no difference in the rates of complications, estimated blood loss, or number of lymph nodes obtained. There were also no differences in the rates of adjuvant therapy. Long term, there were no differences in the rates of local, locoregional, and distant recurrence of primary disease between RAND and open procedures. There were also no differences in postprocedure disease-free survival time (KMW p-value = 0.32; HR [of RAND compared with open] = 0.62). Similarly, there were no statistical differences in the overall survival of RAND patients when compared with the open group (75 vs. 58.9 months; HR = 0.11, p = 0.87). This study is the first to report the long-term effectiveness of robot-assisted surgery compared with the traditional, open approach. In addition to well-known cosmetic benefits, robot-assisted surgery may also offer patients a reduction in uncomfortable drains and improved effects from lymphedema. Overall, this study provides initial data that the RAND may be considered as an alternative approach to open surgery.

OP34 Risk of Disease Recurrence and Re-resections in Crohn's Disease Patients Undergoing Primary Bowel Resection: A Population-Based Study

Abstract Background The rate of having a resection for patients with Crohn's disease (CD) have decreased over decades, while the rates of re-resections seem to have been stable around 1/3 in historic cohorts. Re-resection rates might be influenced by targeted therapies. We aimed to investigate the re-resection rates and risk of recurrence in a contemporary cohort and the effect of medical treatment on these parameters. Methods This population-based cohort included all CD patients undergoing primary intestinal resection between 2010 and 2020 in Eastern Denmark, with a background population of 2,730,000 (46% of the Danish population). Individual clinical characteristics, medication, surgical procedures, and complications, as well as imaging, and endoscopy results were collected. Disease recurrence was defined as a colonoscopy with SES-CD≥3, Rutgeerts score ≥2i, inflammation or stenosis on imaging (MRI, CTA, or IUS), fecal calprotectin ≥ 250 mg/kg, starting corticosteroids after resection or re-resection due to disease activity. We characterized the cohort using nonparametric statistics (median, IQR, percentages) and survival analysis. A Cox regression analysis with propensity score incorporating Montreal classification, age, gender, smoking, and types of resection (colon, ileocecal, or small bowel) was conducted to assess the effect of initiating prophylactic biologic treatment within the first year from resection. Results A total of 631 patients had a primary resection due to disease activity, with a median follow-up from time from diagnosis of 118 months (IQR: 69-170) (Table 1). Prior to the first resection 337 (53%) patients received immunomodulators and 249 (39%) biologics; the same numbers post-surgery were 314 (50%) and 264 (42%), respectively. A total of 256 (41%) patients were resected within two years from diagnosis while this proportion increased to 424 (67%) and 533 (84 %) after 5 and 10 years, respectively. Re-resection rates due to disease activity 5 and 10 years after primary resection were 5% and 10%. The median time from primary resection to disease recurrence was 11,3 months (IQR: 4.7-24.8) (Figure 1). Median time from first to second and second to third resection were 37 months (IQR: 15-64) and 38 months (IQR: 26-55), respectively. We found no significant difference regarding prophylactic biologic therapy within the first year of resection (n 45) based on recurrence or re-resection compared to patients not starting biologics within the first year (HR 0.40, 95%CI(0.12-1.34), p=0.14). Conclusion Most patients undergoing primary resection face post-surgery disease recurrence, yet 1 in 4 remain relapse-free for decades. Despite extensive biologic therapy, 15% still require further resections due to disease activity.

The outcomes of patients with kidney failure due to focal segmental glomerulosclerosis (FSGS) in Australia and New Zealand: A cohort study using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA).

The outcomes of patients with focal segmental glomerulosclerosis (FSGS) on kidney replacement therapy (KRT) have not been well described. This study evaluated the outcomes of patients with kidney failure due to FSGS on KRT including dialysis and kidney transplantation. All adult patients with kidney failure who commenced KRT in Australia and New Zealand from 15th of May 1963 to 31st of December 2018 were retrospectively extracted from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Outcomes of patients with FSGS were compared to those with other causes of kidney failure (non-FSGS). 85,052 patients commenced KRT during the study period, of whom 2991 (3.5%) were patients with FSGS. Compared to patients with non-FSGS, patients with FSGS experienced similar mortality on dialysis (adjusted hazard ratio [aHR] 0.98, 95% CI 0.90-1.06, p = 0.55) and following kidney transplantation (aHR 0.92, 95% CI 0.73-1.15, p = 0.47). The risk of first kidney allograft loss was higher in patients with FSGS (aHR 1.20, 95% CI 1.04-1.37, p = 0.01). However, when death was analysed as a competing risk, the survival in both groups was similar (sub-hazard ratio [SHR] 1.09, 95% CI 0.94-1.28, p = 0.26). Patients with FSGS had a longer waiting time for kidney transplantation (aHR 0.92, 95% CI 0.86-0.98, p = 0.02) and experienced an increased risk of disease recurrence in the allograft (aHR 1.73, 95% CI 1.35-2.21, p<0.001). Compared to patients with other forms of glomerular disease, patients with FSGS experienced similar dialysis and transplant patient survival and death-censored rate of kidney transplantation and allograft loss but higher rates of primary kidney disease recurrence. FSGS was associated with similar dialysis and transplant patient survival and death-censored first allograft loss compared to non-FSGS and other forms of glomerular disease.

Evolving challenges with long-term care of liver transplant recipients.

The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.

Recurrent Primary Paget Disease of Vulva with Paget-Like Epithelial Cells in Papillary Dermis: Displaced or Invasion?

While histological diagnosis of Paget disease of vulva is mostly straightforward, identifying and confirming invasion can be challenging. Often invasion is accompanied by epidermal hyperplasia, marked inflammatory response and desmoplastic reaction. Diagnosis of invasion in Paget disease portends a poor outcome. We report findings from a recurrent primary vulvar Paget disease where overall histomorphology of possible invasive disease is unusual and raises a possibility of displacement of Paget cells in the dermis. We compare histology of the index case with known invasive vulvar Paget disease cases retrieved from our pathology archives. Unique histomorphology in the index case suggests a possibility of previous excision related dermal displacement of Paget cells.

Association of Primary Kidney Disease Type and Donor Relatedness With Live Donor Kidney Transplant Outcomes: An Analysis of ANZDATA

There is limited information about the association between primary kidney disease and donor relatedness with transplant outcomes. This study addresses this gap by evaluating clinical outcomes after kidney transplantation in recipients of living donor kidneys as a function of primary kidney disease type and donor relatedness in Australia and New Zealand. Retrospective observational study. Kidney transplant recipients who received allografts from living donors between January 1, 1998, and December 31, 2018, as recorded in the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Primary kidney disease type categorized as majority monogenic, minority monogenic, or other primary kidney disease based on disease heritability as well as donor relatedness. Primary kidney disease recurrence, graft failure. Kaplan-Meier analysis and Cox proportion hazards regression to generate hazard ratios for primary kidney disease recurrence, allograft failure, and mortality. Partial likelihood ratio test was used to examine possible interactions between primary kidney disease type and donor relatedness for both study outcomes. Among 5,500 live donor kidney transplant recipients, majority monogenic (adjusted HR, 0.58, P<0.001) and minority monogenic primary kidney diseases (adjusted HR, 0.64, P<0.001) were associated with reduced primary kidney disease recurrence compared with other primary kidney diseases. Majority monogenic primary kidney disease was also associated with reduced allograft failure (adjusted HR, 0.86, P=0.04) compared with other primary kidney diseases. Donor relatedness was not associated with primary kidney disease recurrence nor graft failure. No interaction was detected between primary kidney disease type and donor relatedness for either study outcome. Potential misclassification of primary kidney disease type, incomplete ascertainment of primary kidney disease recurrence, unmeasured confounding. Monogenic primary kidney disease is associated with lower rates of primary kidney disease recurrence and allograft failure. Donor relatedness was not associated with allograft outcomes. These results may inform pretransplant counseling and live donor selection. There are theoretical concerns that live-donor kidney transplants may be associated with increased risks of kidney disease recurrence and transplant failure due to unmeasurable shared genetic factors between the donor and the recipient. This study analyzed data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and showed that, although disease type was associated with the risk of disease recurrence and transplant failure, donor relatedness did not impact transplant outcomes. These findings may inform pretransplant counseling and live donor selection.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients – a national cancer centre experience

Purpose or objectiveThe COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery.Materials and methodsIn this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel.ResultsSignificantly, there was a reduction of 37–46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines.ConclusionWe recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient’s confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Recurrent primary scrotal extramammary Paget disease: a case report and literature review.

Extramammary Paget disease (EMPD) is a rare malignant neoplasm arising in apocrine gland-rich skin, which may be classified as either of primary or secondary origin. Management of this condition is predominantly surgical, and is often characterised by lengthy diagnostic delays. Complete surgical excision is challenging, and local recurrence is common. Herein, we discuss a subtle presentation of recurrent scrotal EMPD in a 77-year-old male and review the available literature. Although relatively rare, the indistinct nature of this pathology merits special attention from treating surgeons, who are frequently responsible for initial management and follow-up. The risk of distant metastasis and concomitant prognostic implications necessitate a high clinical index of suspicion, and low threshold for definitive biopsy in similar cases.

KiT-GENIE, the French genetic biobank of kidney transplantation.

KiT-GENIE is a monocentric DNA biobank set up to consolidate the very rich and homogeneous DIVAT French cohort of kidney donors and recipients (D/R) in order to explore the molecular factors involved in kidney transplantation outcomes. We collected DNA samples for kidney transplantations performed in Nantes, and we leveraged GWAS genotyping data for securing high-quality genetic data with deep SNP and HLA annotations through imputations and for inferring D/R genetic ancestry. Overall, the biobank included 4217 individuals (n = 1945 D + 2,272 R, including 1969 D/R pairs), 7.4 M SNPs and over 200 clinical variables. KiT-GENIE represents an accurate snapshot of kidney transplantation clinical practice in Nantes between 2002 and 2018, with an enrichment in living kidney donors (17%) and recipients with focal segmental glomerulosclerosis (4%). Recipients were predominantly male (63%), of European ancestry (93%), with a mean age of 51yo and 86% experienced their first graft over the study period. D/R pairs were 93% from European ancestry, and 95% pairs exhibited at least one HLA allelic mismatch. The mean follow-up time was 6.7 years with a hindsight up to 25 years. Recipients experienced biopsy-proven rejection and graft loss for 16.6% and 21.3%, respectively. KiT-GENIE constitutes one of the largest kidney transplantation genetic cohorts worldwide to date. It includes homogeneous high-quality clinical and genetic data for donors and recipients, hence offering a unique opportunity to investigate immunogenetic and genetic factors, as well as donor-recipient interactions and mismatches involved in rejection, graft survival, primary disease recurrence and other comorbidities.

Analysis of causes of graft loss in 135 kidney transplant recipients

To investigate the causes of graft loss in kidney transplant recipients. We retrospectively analyzed the clinical data of 135 recipients with graft loss after renal transplantation in the Eighth Medical Center of Chinese PLA General Hospital from January 1, 2002 to January 1, 2022. A total of 135 kidney transplant recipients experienced graft failure. The causes of graft loss included graft rejection (70 cases, 51.8%), death of the recipients with functional graft (37 cases, 27.4%), surgical complications (12 cases, 8.9%), drug toxicity (4 cases, 3.0%), carbapenem-resistant Klebsiella pneumoniae infection (4 cases, 3.0%), polyoma BK virus-related nephropathy (3 cases, 2.2%), primary nonfunctioning kidney (2 cases, 1.5%), recurrence of primary disease (2 cases, 1.5%), and prerenal acute renal failure (1 case, 0.7%). The main cause of graft loss after renal transplantation is graft rejection, and the secondary cause is death of the recipient with functional graft, and other reasons can be rare.

MRD Monitoring of Non-DTA Genes By Digital Droplet PCR in the Early Period after Allogeneic Hematopoietic Stem Cell Transplantation Can Effectively Predict Patients at High Risk of Relapse

Background: Hematological malignancies relapse is the major cause of death after allogeneic hematopoietic stem cell transplantation (HSCT). The detection of measurable residual disease (MRD) after HSCT is the effective and important predictor of relapse. Digital droplet polymerase chain reaction (ddPCR), as the third generation PCR, is a novel technology for absolute quantification of nucleic acids developed in recent years. Compared with real-time quantitative PCR (qPCR, first generation) and next-generation sequencing (NGS), ddPCR has better sensitivity, specificity and repeatability, which provide a new platform for the detection of MRD. The purpose of this study was to evaluate whether early MRD monitoring by ddPCR after HSCT can effectively predict the recurrence of primary disease. Methods: We retrospectively analyzed patients with hematological malignancies who underwent allogeneic HSCT and monitored post-transplant MRD by ddPCR at the BMT Center of the First Affiliated Hospital of Zhejiang University School of Medicine from August 2018 to February 2021. Patients who met the following criteria were included in our study: (1) at least one hematological tumor-associated mutations or fusion genes for MRD monitoring at the time of diagnosis; (2) underwent allogeneic HSCT and the stem cell engraftment was successful; (3) received bone marrow MRD detection by ddPCR at least once in the early period (+30 days to +120 days) after HSCT; (4) bone marrow morphology was in remission status within +30 days to +120 days. Results: 100 patients were included in our study. The median follow-up time of patients was 20 months (range 5-46), and the median age was 41 years (range 14-67). Among them, 59 (59.0%) were male, and the most frequent primary diseases were AML (N=59, 59.0%), ALL (N=21, 21.0%), MDS (N=16, 16.0%), respectively. A total of 43 (43.0%) patients were found to be MRD+ after HSCT by early ddPCR detection. The difference in the 2-year cumulative incidence of relapse (2y CIR, 32.5% vs. 19.6%, P= 0.103), 2-year relapse-free survival (2y RFS, 67.0% vs. 79.8%, P=0.110), and overall survival (OS, 63.0% vs. 84.1%, P=0.566) between the MRD+ and MRD- groups were not statistically significant. 30 patients had at least one mutation related to clonal hematopoiesis gene: DNMT3A, TET2, and ASXL1 (DTA), whereas 97 patients had at least one non-DTA gene. When DTA group and non-DTA group were considered separately, MRD+ were 33.3% in DTA gene group and MRD+ were 36.1% in non-DTA gene group. The 2y CIR (0% vs. 21.5%, P=0.160), 2y RFS (100% vs. 78.5%, P=0.170) and OS (90.0% vs. 85.0%, P=0.737) after HSCT was not statistically different between DTA MRD+ group and DTA MRD- group, suggesting that DTA was not suitable as monitoring genes for relapse after transplantation. However, in the non-DTA group, patients with MRD+ had higher 2y CIR (39.8% vs. 18.4%, P=0.014) and inferior 2y RFS (60.2% vs. 80.8%, P=0.017) compared with MRD- patients. To explore whether ddPCR and multiparameter flow cytometry (MFC) can complement each other and further improve the prediction accuracy of relapse, we conducted a joint analysis on the bone marrow MRD detected simultaneously by non-DTA ddPCR and MFC, and divided into four parts: ①MFC MRD+ and non-DTA MRD+ (F+/M+, n=7); ②MFC MRD- and non-DTA MRD+ (F-/M+, n=26); ③MFC MRD+ and non-DTA MRD- (F+/M-, n=8); ④MFC MRD- and non-DTA MRD- (F-/M-, n=56). The sensitivity of ddPCR was higher than that of MFC. The 2y CIR of the four groups was (F+/M+ 71.4% vs. F-/M+ 34.5% vs. F+/M- 53.1% vs. F-/M- 12.2%, P<0.001), and the 2y RFS was (F+/M+ 28.6% vs. F-/M+ 65.5% vs. F+/M- 46.9% vs. F-/M- 87.3%, P<0.001) and OS was (F+/M+ 31.3% vs. F-/ M+ 61.8% vs. F+/M- 87.5% vs. F-/M- 83.8%, P=0.219). Through multivariate analysis, F+/M+ is an independent risk factor for relapse after HSCT (hazard ratio, 9.531, 95%CI, 2.884 to 31.496). It suggested that F+/M+ detected in the early stage after transplantation had higher CIR and inferior RFS. Conclusion: MRD monitoring for non-DTA gene in the early period after HSCT based on ddPCR has a prognostic effect on the recurrence of primary disease and overall survival after transplantation. When ddPCR is combined with MFC to monitor MRD, it is more accurate in predicting relapse and may help instruct preemptive treatment and then reduce the risk of relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Radiologic findings of biliary complications post liver transplantation.

Liver transplantation is a potentially curative treatment for patients with acute liver failure, end-stage liver disease, and primary hepatic malignancy. Despite tremendous advancements in surgical techniques and immunosuppressive management, there remains a high rate of post-transplant complications, with one of the main complications being biliary complications. In addition to anastomotic leak and stricture, numerous additional biliary complications are encountered, including ischemic cholangiopathy due to the sole arterial supply of the bile ducts, recurrence of primary biliary disease, infections, biliary obstruction from stones, cast, or hemobilia, and less commonly cystic duct remnant mucocele, vanishing duct syndrome, duct discrepancy and kinking, post-transplant lymphoproliferative disorder, retained stent, and ampullary dysfunction. This article presents an overview of biliary anatomy and surgical techniques in liver transplantation, followed by a detailed review of post-transplant biliary complications with their corresponding imaging findings on multiple modalities with emphasis on magnetic resonance imaging and MR cholangiopancreatography.

Analysis of 42 cases of childhood superior vena cava syndrome associated with mediastinal malignancy

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.

Ultra-Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer: Clinical Outcomes, Patterns of Recurrence, Feasibility of Definitive Salvage Treatment, and Competing Oncological Risk.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan–Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local–regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07–1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19–6.15). Definitive local salvage therapies were feasible in the majority of the patients with local–regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients’ survival compared to primary disease recurrence.

Recurrence of primary disease following lung transplantation.

Lung transplant has become definitive treatment for patients with several end-stage lung diseases. Since the first attempted lung transplantation in 1963, survival has significantly improved due to advancement in immunosuppression, organ procurement, ex vivo lung perfusion, surgical techniques, prevention of chronic lung allograft dysfunction and bridging to transplant using extracorporeal membrane oxygenation. Despite a steady increase in number of lung transplantations each year, there is still a huge gap between demand and supply of organs available, and work continues to select recipients with potential for best outcomes. According to review of the literature, there are some rare primary diseases that may recur following transplantation. As the number of lung transplants increase, we continue to identify disease processes at highest risk for recurrence, thus shaping our future approaches. While the aim of lung transplantation is improving survival and quality of life, choosing the best recipients is crucial due to a shortage of donated organs. Here we discuss the common disease processes that recur and highlight its impact on overall outcome following lung transplantation.

Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/β-catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of β-catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked β-catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for β-catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n = 11) had a greater percentage of samples with nuclear, transcriptionally active β-catenin (average 58.8%) than those with no recurrence (n = 10; 40.53%), while non-recurrence is correlated with β-catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. β-catenin score and years-to-endpoint are both strongly associated with recurrence status (p = 0.017 and p = 0.00063, respectively). Finally, there was significant association between higher β-catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, β-catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants.

The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.

PSC recurrence post liver transplantation: retransplantation justified or not?

Post-liver transplant (LT), primary disease recurrence is a major cause of graft failure and long-term patient mortality (1). For decades, hepatitis C virus (HCV) recurrence was the number one cause of graft loss (2); however, with the development of potent anti-viral therapy, HCV transplant recipients no longer experience graft loss and death. In contrast, recurrence of autoimmune disease - particularly Primary Sclerosing Cholangitis (PSC) - remains a valid concern for the liver transplant community. This is despite an excellent short-term outcome post LT, with a survival rate above 90 % within the first year after transplant (3).

Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas.

AimsCell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.MethodsMatched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).ResultsCell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases.ConclusionThis work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings.Cite this article: Bone Joint Res 2021;10(9):602–610.