Successful Salvage Research Articles

Management of Hyperleukocytosis in Pediatric Acute Myeloid Leukemia Using Immediate Chemotherapy without Leukapheresis, in Protocol NOPHO-DBH AML-2012

Introduction: Hyperleukocytosis (HL) in pediatric acute myeloid leukemia (AML) is associated with severe complications and inferior outcome. Initial management is subject to debate, and the role of invasive methods such as leukapheresis (LA) and exchange transfusion (ET) has been questioned. We report the results on HL patients included in the NOPHO-DBH AML 2012 study. Patients and methods: All patients were treated on the NOPHO-DBH AML 2012 protocol. Between January 1 st, 2013 and September 30 th, 2021, 714 patients were diagnosed, of whom 122 (17.1%) had HL, defined as white blood cell count (WBC) ≥100x10 9/L. Sixty-nine patients (9.7%) had WBC ≥200 x10 9/L. Protocol guidelines recommended immediate start of the first chemotherapy course (starting with etoposide [ETO] monotherapy for 5 days at 150 mg/m 2 once daily) followed randomized by either cytarabine/mitoxantrone (MEC) or cytarabine/daunoxome or daunorubicin (D[x]EC). The use of LA, ET, or prephase chemotherapy (PCT) was discouraged. In addition to registered data, we sent out questionnaires asking for additional detailed information on HL patients. Results: HL patients had a median WBC of 211x10 9/L (range 101-880). They did not differ from Non-HL patients in terms of age, sex or CNS involvement, but had a higher proportion of extramedullary tumors (18% vs 11%). They had a significantly lower frequency of RUNX1::RUNX1T1 fusions (1.7% vs. 15.4%), and a higher proportion of KMT2A rearrangements (except KMT2A:: MLLT3) (23.1% vs. 12.2%), and FLT3-ITD without NPM1 mutation (20.7% vs. 8.1%). Of the 122 HL patients, 111 (90.2%) were treated according to the guidelines with ETO upfront. LA was used in six patients (4.9%), in one case combined with ET. One of the LAs was performed in a patient unresponsive to ETO (increasing WBC after 2 days of ETO treatment). Eight patients received prephase chemo (various regimes) before start of the first course. In the 111 patients treated with ETO upfront, the first dose ETO was applied the same day as the AML diagnosis or the day after in 94.4%, and the drug was administered via peripheral veins in 37.8% of patients without major complications. After initiation of ETO, the remaining WBC on days 2-5 was 69.0%, 35.6%, 17.2% and 8.4% respectively, of the value before chemotherapy (Figure 1). On day 3, 80.9% had a WBC<100 x10 9/L. Compared to the non-HL group, HL patients had a trend to higher early death rate within the first 6 weeks (5/122, 4.1% vs. 13/592, 2.2%, P=0.062), and a higher rate of resistant disease defined as > 5% blasts after 2 induction courses (14/122, 11.5% vs. 23/592, 3.9%, P=0.002). Five-year event-free survival (EFS) for all HL patients was 51.9±4.8 compared to 64.7±2.1 in the non-HL group. Overall survival (OS) was 73.5±4.2 and 78.7±1.8, respectively (log rank 0.089). Three children with HL died within 2 weeks from diagnosis (2.5%). Early death within 6 weeks occurred in 3/111 (2.7%) in the ETO-upfront group and 2/11 (18.2%) in the LA/ET/PCT group, P=0.064). Of 69 patients with WBC >200 x 10 9/L, 14 patients died, but only three during the first 6 weeks. Conclusions: The NOPHO-DBH AML 2012 protocol is very effective in pediatric AML. The first chemotherapy course starts with five consecutive days of ETO monotherapy. We made use of this “ETO-window” in the management of HL patients, omitting invasive methods to reduce high WBCs. We conclude that in HL patients immediate ETO-therapy without LA/ET is feasible, easy to administer, safe and effective. Treatment results were excellent in terms of early death and OS. The significantly lower EFS for HL patients is explained mainly by a higher frequency of resistant disease, probably due to the higher proportion of high-risk AMLs (low rate of RUNX1:: RUNX1T1, high frequency of rearranged KMT2A and FLT3-ITD/NPM1wt). However, OS was not significantly lower for the HL group, which may be explained by successful salvage of patients with resistant disease or relapse using stem cell transplantation. WBC reduction during the first days of ETO therapy is comparable to reported results of LA, and outcome seems at least equivalent to studies using LA as part of their recommended therapy. Since the ETO-window allows avoiding invasive, costly and time-consuming procedures, the consortium now called NOPHO-DB-SHIP decided to stick to the same policy in the new protocol, CHIP-AML22.

Successful Salvage Therapy With a High Dose of Furmonertinib in a Case of Lung Adenocarcinoma Harboring EGFR Exon 20 Insertion.

Successful Salvage Therapy With a High Dose of Furmonertinib in a Case of Lung Adenocarcinoma Harboring EGFR Exon 20 Insertion.

Transaxillary Capsulorrhaphy with Reimplantation to Correct Bottoming-Out Deformity in Breast Mycobacterial Periprosthetic Infection: A Case Report with Literature Review.

Augmentation mammoplasty is one of the most popular cosmetic surgeries, but there is a high reoperation rate (29.7%) commonly due to capsular contracture, implant malpositioning, infection, and unsatisfactory size. Although infection only accounts for 2% of cases, its management is very challenging, especially with nontuberculous mycobacteria (NTM) infection. Breast prosthetic NTM infection is a rare but is a disastrous condition with an incidence of approximately 0.013%. Immediate salvage reimplantation is usually not suggested, and most studies recommend a gap of 3 to 6 months after combination antibiotics therapy before reimplantation. However, delayed reimplantation often leads to great psychological stress and struggle between the doctor and patient. We present the case report of successful reimplantation in treating prosthetic NTM infections in a 28-year-old female. We discuss a novel technique "transaxillary capsulorrhaphy" to correct the bottoming-out deformity. One year after the combination of antibiotics and surgery, the follow-up computed tomography scan showed complete remission of NTM without recurrence. We discuss the surgical technique in detail. The 1-year follow-up assessment (photos and dynamic video) revealed good cosmesis and reliable correction using the new technique. This report is the first formal description and discussion of one-stage reimplantation following NTM infections. Transaxillary capsulorrhaphy allows for a successful salvage operation when an implant is displaced. This approach provides highly favorable result in eastern women undergoing revision augmentation mammoplasty. This study reflects level of evidence V, considering opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

Use of prostaglandin and cyclophosphamide for pediatric lupus with digital gangrene: Back to safety before hitting the axe!

Digital gangrene is a rare presenting feature of childhood lupus and only a reported incidence of 1.3%. We describe two cases of pediatric onset systemic lupus erythematosus (SLE), both 16years old, presenting with digital gangrene and the successful salvage of the digits after using intravenous cyclophosphamide for immunosuppression and use of intravenous prostaglandin E1 infusions for limb reperfusion. Both of the patients responded exceptionally to the infusions with resolution of gangrene and near-total preservation of the functionality of toes.

Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia.

Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.

Salvage Abdominoperineal Resection for Locally Recurrent or Persistent Anal Squamous Cell Carcinoma after Definitive Chemoradiation.

Initial treatment for patients with squamous cell carcinoma of the anal canal includes definitive chemoradiation. Salvage abdominoperineal resection (APR) is the treatment of choice for recurrent or persistent disease. Older studies suggest approximately 50% successful salvage of recurrent or persistent disease with APR. Risk factors for failure after salvage APR are incompletely characterized. Using a single institutional database, patients were identified who underwent salvage APR after definitive intensity-modulated radiotherapy-based chemoradiation between 2003 and 2022. Clinical and pathologic variables analyzed included age at APR, sex, race, HIV status, initial cT stage, initial cN stage, radiation dose, recurrent vs persistent disease, recurrent pT stage, recurrent pN stage, the presence of LVSI, PNI or <2mm surgical margins, and the use of either intraoperative radiation or another treatment modality in addition to APR. The log rank test was used to determine differences in time from APR to events (local recurrence, distant metastasis and death) based on clinical and pathologic variables. The Cox Proportional Hazard Model was used to perform multivariable analysis for all factors with a univariate P-value <0.1. Of 628 patients with anal squamous cell carcinoma, 50 (8.0%) were treated with abdominoperineal resection for locally recurrent (n = 29, 58%) or locally persistent (n = 21, 42%) disease. Median [interquartile range] follow up was 40.0 months [15.2-68.0 months] from APR. Median local recurrence-free survival was not reached; 1- and 2-year local recurrence-free survival was 81% (95% CI 72-92%) and 76% (64-89%). On multivariable analysis, pathologic T-stage of the recurrence (3.85 (1.07-13.9); P = .040), the presence of lymphovascular space invasion (9.1 (1.12-73.62); P = .038) and surgical margins <2mm (8.81 (2.11-36.73); P = .003) were all significantly associated with higher rates of local recurrence. Median distant metastasis-free survival was not reached; 1- and 2-year distant metastasis-free survival was 88% (81-98%) and 79% (67-92%). On multivariable analysis, only persistent (versus recurrent) local disease was significantly associated with higher rates of distant metastasis (1.23 (1.05-5.55) P = .043). Median overall survival was not reached; 1- and 2-year overall survival was 90% (81-98%) and 78% (65-90%). On multivariable analysis, only recurrent pT stage (T3/4 vs T1/2) was associated with higher rates of death (5.87 (1.02-33.65); P = .047). APR is a successful salvage modality for anal squamous cell carcinoma with recurrent or persistent disease after chemoradiation results. Patients with pT3/4 disease, lymphovascular space invasion, surgical margins <2 mm may be associated with higher re-recurrence rates and may benefit from more frequent monitoring or treatment escalation.

Successful Limb Salvage Reconstruction Using Bulk Femoral Head Allograft

Category: Ankle Introduction/Purpose: The use of femoral head allografts in salvage surgeries for lower extremity reconstruction help address surgical problems of large bone deficits. There are very few publications and mixed results in the literature as to the outcomes of this salvage procedure. These limb salvage procedures involve significant surgical complexity with the end goal of retaining a stable, brace-able lower extremity. The purpose of this retrospective review is to report the results and utility of bulk femoral head allograft for limb salvage including time to weight bearing, CT confirmed fusion time, reoperation rates, and ultimate limb salvage success. Additionally, this article categorizes femoral head surgical preparation, adjunct biologics use, fixation constructs, and dissection techniques used. Methods: Patients who underwent reconstructive limb salvage surgery using femoral head allografts over a 5-year period (2015- 2020) were identified. The surgeries were among 5 different fellowship-trained surgeons at a single institution. Indications included post-traumatic AVN, Charcot ankle, revisional surgery, and failed total ankle replacement. Femoral heads were used in either ankle fusions alone or in tibiotalocalcaneal fusion. Time to weight bearing, CT fusion time, reoperations, and ultimate limb salvage were recorded. Reoperations were reported minor if involved partial HWR, superficial I&amp;Ds, or exostosis/HO removal. Major reoperations were defined as full revision surgery/failure of femoral head construct, placement of antibiotic rods for deep infection, or BKA. Limb salvage was defined as being successful if the patient was walking with or without bracing at the last follow-up. Results: Twenty-three cases were identified with 13 performed for failed total ankle replacements, 7 post-traumatic avascular necrosis of the talus, and 3 neuropathic Charcot ankles. The average radiographic follow-up time was 665 days with an average time to weight bearing of 86.48 days. 18/23 patients had CT confirmation of femoral graft union with an average time to union of 461.92 days. 9 patients were found to have less than 50% graft incorporation at the last follow-up. There were 9 reoperations recorded, 8 minor and 1 major. All patients were chart documented stable with independent weight bearing either with or without a brace on the last clinic follow-up. Conclusion: Limb salvage in cases of large bone defects can be very challenging. We report a high success rate of limb salvage using bulk femoral head allograft. Complete fusion of bulk femoral head allograft although desirable, was not necessary to maintain limb salvage in this retrospective study. Patients were able to weight bear and maintain the integrity of the bulk allograft despite the lengthy time to achieve fusion in cases where fusion was achieved. This study highlights that bulk femoral head allograft can offer excellent salvage options with a high degree of success in complex limb salvage reconstruction.

Treatment of Recurrent Orbital Rhabdomyosarcoma with Exenteration and HDR Brachytherapy in a Custom Mold

Rhabdomyosarcoma (RMS) is the most frequent cancer affecting the orbit in children. The orbit is classified as a favorable site for RMS as treatment with chemotherapy and radiation is effective. Local failure for patients with RMS of the orbit has ranged from 2-16% on IRS and COG protocols. In the event of local recurrence, survival is poor, and management is difficult. We report four patients with local recurrence of orbital RMS managed with orbital exenteration followed by high dose rate (HDR) brachytherapy. Four patients were treated from 2016-2022. HDR brachytherapy with Ir-192 was delivered in a custom mold of the orbit made after the orbital exenteration procedure. Brachytherapy was given in 6-7 twice daily (BID) fractions starting 1 week after the orbital exenteration. At the time of brachytherapy, patient ages were 3, 1, 7, and 7 years. Three patients had embryonal histology and underwent initial systemic therapy with ARST0331 regimen A. The fourth patient had alveolar, FOXO1 fusion positive RMS and was initially treated as per COG D9803 regimen A. All patients had received proton radiotherapy as part of initial treatment. Three received 50.40 Gy and one received 45 Gy. Patients developed biopsy-proven, recurrent disease an average of 56 weeks (range 38-77) after initial diagnosis. All patients received salvage chemotherapy before undergoing orbital exenteration at an average of 12 weeks after recurrence (range 5-16). Three patients received 30 Gy in 6 BID fractions, and one patient received 28 Gy in 7 fractions with HDR brachytherapy using an Ir-192 source. All four patients are alive without evidence of disease at an average of 27 months (range 6-70) from recurrence and 39 months (range 21-78) from initial diagnosis. All patients have acceptable orbit healing. Two patients have asymptomatic evidence of frontal lobe edema (and in one case possible necrosis) extending 1-2 cm above the orbit. This appears to be beyond the range of the brachytherapy dosimetry, but the combination of proton beam and brachytherapy are implicated. No other toxicities have occurred. Orbital RMS has a favorable prognosis, but local failure after initial combined modality therapy can be fatal. Options for successful local salvage are limited. Orbital exenteration with HDR brachytherapy in a custom mold is an effective and safe procedure for local control in these difficult cases.

Outcomes of Watch and Wait Following Total Neoadjuvant Therapy for Rectal Cancer

To evaluate the outcomes of patients with locally advanced rectal cancer who achieved a clinical complete response (cCR) after total neoadjuvant therapy and enrolled in a prospective watch and wait (WW) database. Consecutive patients with locally advanced rectal cancer who achieved cCR following total neoadjuvant therapy (long-course chemoradiotherapy plus systemic chemotherapy) and were enrolled in our institutional WW surveillance protocol from 2014 through 2022 with the intention of organ preservation. Patients with lack of follow up according to our institutional protocol were excluded. Primary outcomes included local tumor regrowth and distant metastatic disease recurrence. Thirty-three consecutive patients (48% male; median age 61 [33-77] years) with the diagnosis of locally advanced rectal adenocarcinoma were managed by a multidisciplinary team. All patients had Eastern Cooperative Oncology Group Performance Status score of 0 or 1 at time of rectal cancer diagnosis. Location of tumor included upper rectum (18%), middle rectum (40%), and lower rectum (42%). On initial staging magnetic resonance imaging, 4 (12%) patients had evidence of extramural venous invasion, 6 (18%) had a threatened mesorectal margin, and 4 (12%) had anal sphincter or levator ani tumor involvement. A majority (61%) received chemotherapy followed by long-course chemoradiotherapy. Only one patient had an unplanned break during radiotherapy. Local tumor regrowth was diagnosed in 4 (12%) patients and all underwent successful salvage surgery without additional local failures at a median follow-up of 19 [12-48] months. Two of these four patients remain disease-free at a median follow-up time of 12.5 months. Mean time to local tumor regrowth as first site of cancer recurrence was 33.5 [18-46] months. Distant metastatic disease as the first site of recurrence occurred two patients (6%). Mean time to distant metastatic disease as first site of recurrence was 27 months. Only one mortality occurred in the entire group at a median follow-up of 49 [8-102] months. Organ preservation after total neoadjuvant therapy for locally advanced rectal cancer yields excellent outcomes with low local and distant relapse rates. Structured surveillance protocols and multidisciplinary care are essential for success.

A Phase II Trial Evaluating Rapid Mid-Treatment Nodal Shrinkage to Select for Adaptive Deescalation in p16+ Oropharyngeal Cancer Patients Undergoing Definitive Chemoradiation

The purpose of this study is to determine if rapid mid-treatment nodal shrinkage (RMNS) can identify patients with p16+ oropharyngeal cancer (OPC) who can be safely deescalated with reduced dose chemoradiation therapy (CRT). The primary endpoint was 2-year progression free survival (PFS). Inclusion criteria were as follows: T1-3, N1, M0 (AJCC 8th edition) p16+ OPC with <10 pack-year smoking history. All patients were initially planned for standard dose CRT (70 Gy) and weekly cisplatin. Patients were evaluated with a CT scan at week 4 for RMNS, defined as >40% nodal volumetric reduction from baseline. If RMNS was achieved, they proceeded to deescalated CRT (60 Gy). If not, they received standard CRT. Biomarker correlates were collected at baseline and week 4 of CRT including plasma TTMV (tumor tissue modified viral) HPV DNA and MRI diffusion weighted imaging (DWI). Univariate logistic regression analyses (UVA) were performed to evaluate predictors of RMNS. Odds ratios with 95% CI are reported, using a p<0.05 for statistical significance with a two-sided test. Wilcoxon rank sum tests were used to evaluate differences between the two groups using p < 0.05, 2-sided) for statistical significance. All statistical procedures were performed using R () with no adjustments for multiple testing. Thirty-six patients were enrolled: median age: 60 years; 81% male; primary site: 36% base of tongue, 53% tonsil, 11% both; T-stage: 39% T1, 50% T2, 11% T3; N-stage: 100% N1; any smoking history: 58% yes, 42% no; 67% (n = 24) had RMNS and received deescalated CRT while the remaining proceeded to standard CRT. At a median follow-up of 32.4 months, 2-year PFS between the standard and deescalated groups were 91.7% vs 90.9%, respectively (p = 0.97). All patients with recurrence underwent successful salvage treatment with 2-year OS 100% for all patients. On UVA, rapid TTMV HPV DNA clearance (baseline to week 4) (OR 12.0 [1.65-250], p = 0.034), lower MRI diffusivity (ADC) at baseline (OR 0.79 [0.61-0.97], p = 0.042) and week 4 (OR 0.76 [0.60-0.91], p = 0.009), and higher MRI diffusional kurtosis at baseline (OR 1.09 [1.01-1.21], p = 0.051) and week 4 (OR 1.24 [1.09-1.52], p = 0.009) were significantly associated with RMNS. When comparing the deescalated and standard cohorts, the mean baseline and week 4 MRI ADC were significantly lower and week 4 MRI diffusional kurtosis was significantly higher in the deescalated group. In this phase II study, rapid mid-treatment nodal shrinkage appeared to select favorable risk p16+ oropharynx cancer patients for treatment de-escalation. Rapid clearance of TTMV HPV DNA at week 4 as well as MRI DWI biomarkers of low ADC and high diffusional kurtosis values were correlated with RMNS. A larger study is planned to incorporate RMNS and biomarkers for further treatment de-escalation. Additional trial information is available at ClinicalTrials.gov (Identifier: NCT03215719).

Extreme Limb Salvage: The Thin SCIP Flap for Distal Amputation Coverage in Highly Comorbid Patients.

Limb length preservation is correlated with overall survival. Successful free flap coverage of forefoot, midfoot, and hindfoot amputations can prevent more proximal below-knee amputations but is challenging in patients with multiple comorbidities. The thin superficial circumflex iliac artery perforator (SCIP) flap is well-suited for these patients, as it provides thin, pliable tissue from a favorable donor site. A retrospective review of all patients with distal amputations requiring coverage with a thin SCIP flap between 2016 to 2022 was performed. Patient demographics, amputation levels, and wound characteristics in addition to flap and microsurgery details were analyzed. The primary outcome was limb salvage. Secondary outcomes included partial flap necrosis, flap revision rate, and additional postoperative complications. Thirty-two patients (mean age, 57.3 years) underwent reconstruction of forefoot, midfoot, and hindfoot amputations with thin SCIP flaps (mean follow-up, 36 months). Twenty-eight patients (87.5%) had diabetes, 27 (84.4%) had peripheral artery disease, and 15 (46.9%) were dialysis-dependent. Average flap size was 59.5 cm 2 and average flap thickness was 5.7 mm. Successful limb salvage was achieved in 27 patients (84.3%). Three cases (9.4%) had total flap loss. Twenty-one flaps (65.6%) had partial necrosis, of which 12 (57.1%) healed with conservative management and 7 (33.3 %) healed after late revision. The thin SCIP flap is a useful option for coverage of distal pedal amputations in patients with significant comorbidities. Despite higher rates of partial flap necrosis, free flap reconstruction allowed for high rates of limb salvage in a challenging patient population. Therapeutic, IV.

Success of transmetatarsal amputation for limb salvage in patients with peripheral artery disease.

Limb salvage is a difficult path for patients to travel as there is no guarantee of the outcome, often the major factor is perfusion. For patients who underwent transmetatarsal amputation (TMA), success rate is crucial as the next option is most likely a major amputation. We performed a 10 years (2010-2020) retrospective review of patients that underwent a TMA and had an angiogram or computed tomography angiography (CTA) perioperatively at the Dallas VA Medical Center. Failure after TMA was defined as a patient requiring a proximal amputation within 1 year. There were 125 TMAs performed between 2010 and 2020 at the institution. Forty-four (35.2%) patients had an angiogram/CTA peri-operative and met the inclusion criteria. Seventeen subjects (38.6%) had a higher level of amputation. Of the 17 failures, 2 (11.8%) patients had no patent vessel runoff to the foot, 9 (52.9%) had one vessel, 4 (23.5%) had two vessels, and 2 (11.8%) had three vessels runoff. One vessel runoff to the foot yielded a high rate of poor outcomes (56.3%) defined as a higher level of amputation. Two or more vessels runoff to the foot had over 75% success of limb salvage with a TMA.

Daptomycin as an option for lock therapy: a systematic literature review.

Aim: To review preclinical and clinical data relevant to daptomycin lock therapy in catheter-related bloodstream infection (CRBSI). Methods: Systematic review in PubMed, Scopus and clinical trial registries. Results: Preclinical data demonstrate daptomycin lock solution stability and compatibility with heparin, good biofilm penetration, bactericidal activity against biofilm-embedded bacteria, and high efficacy invitro and in animal catheter infection models. Clinical data remain limited (two case reports and five case series totaling n=65 CRBSI episodes), albeit promising (successful catheter salvage in about 80% of cases). Conclusion: Despite theoretical advantages of daptomycin, clinical data remain scarce. Comparative studies versus alternative lock solutions are needed, as well as studies to define optimal daptomycin lock regimen (including optimal concentration, dwell time and lock duration).

Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acquired Hypocellular Bone Marrow Failure

Children with acquired hypocellular bone marrow failure of unknown cause (AHBMF) are usually diagnosed either with severe aplastic anemia (SAA) or refractory cytopenia of childhood (RCC). Patients with AHBMF who lack a matched donor and who failed or relapsed after immunosuppressive therapy (IST) need alternative therapies. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) offers a curative treatment for these patients. We report a multicenter Spanish experience with haplo-HSCT in pediatric patients with AHBMF. Eleven pediatric patients (SAA, n=9; RCC, n=2) underwent haplo-HSCT with different lymphodepletion strategies. Most patients (10 of 11) had previously failed to respond or relapsed after IST. The conditioning regimen was reduced intensity in SAA and myeloablative in RCC. Patients with SAA received low-dose radiotherapy as part of their conditioning regimen. All patients engrafted. Viral reactivation was common (8 of 11). Acute GVHD grade ≥II was seen in 5 patients. Chronic GVHD was diagnosed in 4 of the long-term survivors. Transplantation-associated microangiopathy was a frequent complication in SAA patients and was related to worse outcome. Two patients died of transplantation-related complications. Overall survival was 81%, with a median follow-up of 36 months. Haplo-HSCT can be a successful salvage curative treatment for pediatric patients with AHBMF, but with significant toxicities that must be addressed. Transplantation-associated microangiopathy was the most critical complication.

Testicular Torsion: An Analysis of Rural Geography and Socioeconomic Status

ObjectivesTesticular torsion is a time-critical, organ-threatening diagnosis requiring prompt surgical intervention for successful salvage of the organ. In Australia, 28% of individuals live in rural and remote areas and face barriers to health care such as greater distance, lower socioeconomic status, (SES), and limited health infrastructure. We hypothesize that these barriers would delay intervention and access to surgical care, and lead to higher orchidectomy rates.ObjectivesA 12-year retrospective audit was conducted at a large rural referral center in Australia, focusing on patients undergoing scrotal exploration for testicular torsion. Primary outcomes were orchidectomy rate, time to operation, and ultrasound (US) and their relationship with patient distance, SES, age, and peripheral hospital attendance. Data on SES for geographic postcodes was obtained from the Australian Government Socio-Economic Indexes for Areas 2016. Statistical analysis was performed using IBM SPSS Statistics software, and a P value &lt; 0.05 was considered significant.ResultsThe study involved 107 patients, of whom 46% had left-sided pathology. The median age of the patients was 14 years. Median SES was in the 37% to 41% centile range, median distance from travelled was 62 kilometers, and median time to operation from triage was 194 minutes. Of the patients, 34 attended a peripheral hospital. No significant risk factors for orchidectomy were identified. US was used in 65% of cases, with torsion detected in 50% of those cases, and orchidectomy performed in 11 patients. US had a sensitivity of 86.1% and specificity of 52.9%.ConclusionDespite significant differences in geographical distance, SES, age, and access to health care, patients in rural and remote areas of Australia experienced equivalent outcomes in testicular torsion management. Testicular torsion was safely managed at a central referral center using a peripheral hospital catchment in rural and remote areas of Australia, despite significant time delays due to greater distance or lower SES.

MDB-12. TRANS-SPECIES ANALYSIS OF REPLICATION-REPAIR DEFICIENT (RRD) MEDULLOBLASTOMA AND RESPONSE TO IMMUNE-CHECKPOINT INHIBITION: AN IRRDC REPORT

Abstract BACKGROUND Replication-repair deficiency (RRD) stemming from mismatch repair and polymerase-proofreading gene defects (MMRD/PPD) lead to hypermutant childhood cancers, most frequently brain tumors. While medulloblastoma is reported, the clinical, genomic and immune landscape remains unknown. METHODS We analysed the genome, methylome, transcriptome (bulk, single-nuclei) and immune-microenvironment of the largest cohort of RRD-medulloblastoma patients enrolled by the International RRD Consortium, and correlated these to clinical outcomes. RRD mice-models were used to preclinically assess response to immunotherapy. RESULTS RRD-medulloblastoma (n=40) were enriched for anaplasia (55%) and localised disease (85%). Methylation/nano-string-based subgrouping failed to classify 40%, while the remaining clustered with the SHH-subgroup. Copy-number changes were notably infrequent (&amp;lt;20%). All tumors harboured hypermutation and microsatellite instability in contrast to non-RRD controls (p&amp;lt;0.0001). Pathogenic variants were frequent in POLE/POLD1 (80%), TP53 (48%) and SHH-pathway genes (PTCH1, SUFU, SMO: 56%). Interestingly, some tumors additionally had glioma-driver alterations (ATRX, NF1: ~50%), similar to RRD cerebellar glioblastoma, but distinct from both non-RRD medulloblastoma (n=791) and hemispheric glioblastoma (n=733) controls. Moreover, although bulk-transcriptome matched non-RRD SHH-medulloblastoma, single-nuclei analyses suggested an earlier cell-of-origin potentially explaining the heterogenous phenotypes resulting from the driver mutations. Uniquely, immune analyses (gene expression and immunohistochemistry) demonstrated high intra-tumoral CD8 T-cell infiltration. Three-year progression-free survival was 60%. Outcome was worse for RRD-medulloblastoma harbouring TP53-mutation (p=0.04) and failing subgroup-classification (p=0.004). Nestin/Cre MSH2-/- POLE;p.S459F mice developing medulloblastoma recapitulated human disease and demonstrated response to anti-PD1 monotherapy. Recurrent/progressive human tumors including those harbouring TP53-mutations exhibited radiological responses to anti-PD1 monotherapy, which was associated with prolonged ongoing survival in comparison to those not treated with checkpoint-inhibitors (p=0.02). CONCLUSIONS Hypermutant RRD-medulloblastoma reveal heterogenous phenotypes due to unique spectrum of driver mutations and an early cell of origin. Their immune-hot microenvironment allows successful salvage treatment with checkpoint-inhibitors for those failing chemo-radiation, including the high-risk SHH/TP53-mutant and unclassified subgroups.

A prospective evaluation of pelvic radiation vs. no radiation among patients with young-onset rectal cancer: Impact on patient-reported outcomes.

3618 Background: The rise in young-onset rectal cancer (YORC) calls for better understanding of the long-term impact of radiation therapy(RT) on gastrointestinal(GI) toxicity and pelvic organ function. We aimed to prospectively capture the longitudinal trajectories of patient-reported outcomes(PROs) in YORC patients who received RT vs. no RT and to identify factors associated with unfavorable PROs. Methods: We prospectively enrolled 120 YORC patients undergoing curative-intent treatment. The validated EORTC QLQ-CR29 was self-administered at time intervals grouped as: 0-11 months, 12-23 months, and 24+ months post-resection. Responses were stratified by receipt of neoadjuvant RT (yes vs. no). The longitudinal change in PROs was described by a linear mixed effects model. Multivariate linear regression was used to determine the impact of treatment factors on long-term PROs. Results: The median age at diagnosis was 44. The majority (N = 92, 77%) presented with cT3,4/N+ disease. Preoperative therapy included: no RT (N = 38, 32%; 8 [7%] who received chemotherapy alone, and 30 [25%] who received no neoadjuvant therapy), vs. RT (N = 82, 68%; where 59 [72%] also received concurrent capecitabine). More patients in the RT group had advanced T stage (3 or 4; 94% vs. 56%, P&lt; 0.001), distal tumor (median 7 vs. 12.5 cm from the anal verge, P&lt; 0.01), and underwent abdominal perineal resection (19 vs. 0%, P&lt; 0.001). After a median follow-up of 70 months, all were alive: 103 (86%) were disease-free, 9 (8%) had recurrence with successful salvage, and 8 (7%) had disease progression. In the RT group, sore skin improved at 12-23 and 24+ months (Estimate [ B]: -16.5, P= 0.03 and B: -14.4, P= 0.03), dyspareunia improved at 12-23 months ( B: -31.8, P&lt; 0.01), and blood/mucus in stool improved at 24+ months ( B: -8.01, P&lt; 0.01) vs. 0-11 months. At 24+ months, RT receipt was associated with worse stool frequency ( B: 26.4, P&lt; 0.01), urinary frequency ( B: 18.4, P= 0.04), and flatulence ( B: 23.0, P= 0.02). Conclusions: YORC often require multimodality therapy including RT. Sore skin, dyspareunia, and blood/mucus in stool improved, but flatulence and frequency can persist beyond 2 years post RT. Proactive counseling and supportive measures are needed to inform treatment choices and mitigate long-term impact. [Table: see text]

Percutaneous deep venous arterialization with balloon angioplasty salvaged a life‐threatening critical limb in a hemodialysis patient after repeated pedal angioplasty failed: A case report

AbstractChronic limb‐threatening ischemia (CLTI) with severe below‐the‐ankle (BTA) lesions is often difficult to revascularize with endovascular treatment (EVT) and surgical treatment. We present a case of successful limb salvage using percutaneous deep venous arterialization (pDVA) in a patient with CLTI whose BTA lesion reconstruction failed. A 57‐year‐old man with diabetes mellitus and end‐stage renal failure on maintenance hemodialysis was referred to our hospital because of gangrene in the second and third toes of his left foot. EVT was repeated for the anterior tibial artery, posterior tibial artery (PTA), dorsal foot artery, and plantar artery lesions; however, revascularization below the ankle was unsuccessful. As the infection had spread to the sole of the foot, below‐the‐knee amputation was indicated, but the patient refused. Therefore, we performed pDVA on the left PTA simultaneously with a Lisfranc amputation. An arteriovenous fistula was created at the ankle joint using a Venous Arterialization Simplified Technique and a guidewire was inserted into the plantar vein. Balloon dilatation from PTA to the plantar vein was performed to complete the pDVA. Although repeated EVT was required to maintain blood flow in the pDVA, skin grafting was performed 3 months after the pDVA, the wound completely healed, and he was discharged 6 months after the DVA. The pDVA can be an option for limb salvage in patients with no‐option CLTI who are confronted by imminent amputation.

Management of Epidural and Subgaleal Abscesses in Pediatric Craniosynostosis Surgery

Introduction: Epidural/subgaleal abscesses in craniosynostosis surgery are rare but serious complications that may compromise neurological functioning in pediatric craniofacial populations. We evaluated the risk and evolution of management of post-operative subgaleal/epidural abscesses in craniosynostosis patients treated over 20 years by a single surgeon. Methods: Pediatric patients who underwent transcranial procedures for craniosynostosis by a single surgeon from 1997 to 2018 were included. The patients were stratified into groups based on the development of post-op abscess. The primary outcome measure was bone salvage success. Post-op abscesses were drained in the following manner: either open packing with delayed closure or no elevation of the scalp flap, followed by copious irrigation and deep (epidural) drain placement plus long-term intravenous antibiotics. Results: A total of 384 patients underwent 413 cases in this period: 177 sagittal, 85 unicoronal, 49 metopic, 4 lambdoid, and 69 cases of multiple suture synostosis. In this cohort, epidural/subgaleal abscess were found in 6 patients (1.5%) who all had bilateral fronto-orbital advancement ( P = .03). Bone salvage was attempted in all 6 patients with only minor bone resorption seen in 3 of the patients who presented with abscess. Conclusion: This study found that patients undergoing bilateral fronto-orbital advancement were at increased risk of a deep space infections, while those undergoing clavarial vault remodeling with barrel staves alone, were not. We were able to salvage the bone grafts and prevent neurological sequela with surgical washout, placement of drains and intravenous antibiotic therapy.

Predicting Foot Salvageability in Diabetic Foot Lesion: Comparison of Benin Diabetic Foot Severity Score and Wagner System

BACKGROUND: A diabetic foot lesion is a disabling and chronic complication of diabetes mellitus. It has been found to be relatively common in the University of Benin Teaching Hospital Benin City. An aid for making decision on choice, modality of treatment and prognostication is needful in the management of diabetic foot lesion. Such aid would be more purposeful if at the outset it can state which foot would be salvaged or not. Foot salvageability implies maximal preservation of the foot and avoidance of above ankle amputation. The aim of this study was to compare two classification systems as predictors of foot salvageability in diabetic foot lesion: The Wagner Diabetic Foot Severity Score (WDFSS) and Benin Diabetic Foot Severity Score (BDFSS). METHODOLOGY: A total of 65 patients with diabetic foot lesions admitted in the medical or surgical wards of the UBTH, Benin City, were recruited into the study. All the subjects were diagnosed diabetic using fasting blood sugar value of at least 7mmol/L or higher. Before treatment, the researcher personally examined each patient’s diabetic foot lesion and classified them using both WDFSS and BDFSS. Thereafter, patients were treated with antibiotics based on bacteriological studies, blood sugar control and wound care using basic surgical principles. Daily wound dressing was done using normal saline. During the period of treatment, the patients were evaluated by the researcher at 2 weekly intervals, using the WDFSS and BDFSS. The desired outcomes of treatment included successful foot salvage (avoidance of amputation above the ankle) or failure to salvage the foot ending in below knee amputation. Age, sex, duration of diabetes mellitus, clinical findings of the diabetic foot lesion such as skin colour, ulcer grade, sensation and presence or absence of peripheral pulses, radiological features of the foot and ankle were all documented. The outcome of treatment based on the stage or state of the foot lesion was also noted. The data obtained was analyzed as both descriptive and inferential methods using SPSS version 20.0 statistical software. Logical argument and Receiver Operating Curve were also used. RESULTS: BDFSS had greater AUC of 0.928 than WDFSS with AUC of 0.78. BDFSS recorded a higher degree of 95% confidence interval of 85% to 99% as against WDFSS with 95% confidence interval of 66% to 90%. Also, BDFSS recorded a higher sensitivity 95% as against WDFSS with sensitivity of 79%. Additionally, BDFSS has a greater Specificity of 87% as against WDFSS with Specificity of 73%. A bivariate logistic regression analysis was performed to assess which characteristic and clinical variables were independently associated with outcome using variables with P&lt; 0.01 according to the univariate analysis. CONCLUSION: This study demonstrated that the BDFSS has acceptable accuracy and capacity for predicting diabetic foot lesion outcome. BDFSS in this study was found to be comparable to the WDFSS thereby making it a useful tool in clinical practice and research both for the anticipation of health care cost and for comparing patient subgroups.