Citations

Abstract Background En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. Methods MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. Results There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI = 0.08–0.59; p = 0.003) and risk of death (PHR = 0.31; 95%; CI:0.12–0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR = 0.35; 95%CI = 0.16–0.76; p = 0.009) as well as OS (PHR = 0.25; 95%CI = 0.08–0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR = 0.06; 95%CI = 0.01–0.77; p = 0.030), but not a decreased OS (PHR = 0.50; 95% CI = 0.19–1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95%CI:0.02–1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. Conclusion This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.

Background: Debridement and implant retention (DAIR) has variable success as a treatment for acute periprosthetic joint infection (PJI), with generally poor outcomes reported in the literature 1 . Because of the unacceptably high failure rate of DAIR, we implemented a 2-stage debridement protocol that includes the use of high-dose antibiotic beads between stages for the treatment of acute PJI. In 2 previous studies, with an average follow-up of 3.5 years in each study, we reported overall infection-control rates of 87% and 90% 2,3 . Description: Following exposure of the joint, cultures are obtained, and all modular components are removed, scrubbed, and soaked in an antiseptic solution. A thorough irrigation and debridement with complete synovectomy is performed, followed by temporary reinsertion of the original modular parts. High-dose antibiotic cement beads are inserted into the joint, and the joint is closed. Approximately 5 to 6 days later, a second debridement is performed, the beads are removed, and the new modular, sterile components are implanted. The patient is placed on a course of intravenous and, later, oral antibiotics, in addition to a standard postoperative rehabilitation protocol. Alternatives: Long-term suppressive antibiotic therapy. One-stage DAIR. One-stage exchange arthroplasty. Two-stage exchange arthroplasty. Resection arthroplasty. Amputation. Rationale: The treatment of acute PJI has historically consisted of a single irrigation and debridement, with exchange of modular parts and retention of the components, followed by intravenous antibiotic therapy. Despite having lower rates of patient morbidity compared with a 2-stage exchange arthroplasty, this more traditional procedure also has a higher rate of failure, with reported rates as high as 60% to 84% 4–12 . The utility of component retention continues to be a topic of debate 13 . Alternatives to component retention include both 1- and 2-stage exchange procedures. Although these modalities offer potentially higher rates of infection control, they are associated with substantial patient morbidity, particularly in patients with well-fixed implants 14–16 . Furthermore, exchange procedures may result in substantial iatrogenic bone loss, which can be problematic in revision total joint arthroplasty procedures, in which bone stock may already be limited. The double-DAIR protocol offers infection-control rates that are comparable with those of component-exchange procedures, but with the lower patient morbidity associated with component-retention procedures. Furthermore, the double-DAIR procedure provides the added benefit of retaining important bone stock. Expected Outcomes: The success rate for the double-DAIR procedure has been reproducible, with infection-control rates of 87% and 90% reported in 2 studies from a single cohort at our institution 2,3 . These rates represent a substantial improvement compared with a single irrigation and debridement 1 , and are on par with those reported for 2-stage exchange arthroplasty procedures 17–21 . The infection-control rates of the double-DAIR procedure did not significantly vary depending on whether infection occurred following a total knee or total hip arthroplasty. However, not surprisingly, patients who underwent debridement following a revision procedure had a lower rate of success (77.1% successful infection control) compared with patients debrided following a primary procedure (93.8% successful infection control). We could not demonstrate an association with organism and success or failure of treatment. Although not significant, there was a trend toward an association between the time from symptom onset to initial treatment and infection control (p = 0.07) 2 . Patients with successful infection control underwent the initial debridement an average of 6.2 days after symptom onset, compared with 10.7 days in patients in whom treatment had failed. Several other studies have demonstrated that successful infection control is associated with earlier initial irrigation and debridement 22–27 . We strongly support that, in the setting of confirmed acute PJI, prompt initiation of treatment optimizes the chances for successful infection control. Important Tips: Thorough debridement is key to successful infection control of infection. Antibiotic-loaded bone cement has repeatedly been demonstrated to be safe, and we recommend its use 28–31 . Extended oral antibiotics following debridement with component retention can increase infection-free survivorship 32 .

AbstractBackground and ObjectivesChordomas of the mobile spine (C1–L5) are rare malignant tumors. The purpose of this study was to review the outcome of surgical treatment for patients with primary mobile spine chordomas.MethodsThe oncologic outcomes and survival of 26 patients undergoing surgical resection for a primary mobile spine chordoma were assessed over a 25‐year period. The mean follow‐up was 12 ± 6 years.ResultsThe 2‐, 5‐, and 10‐year disease‐free survivals were 95%, 61%, and 55%. The local recurrence‐free survival was improved in patients receiving en bloc resection with negative margins (83% vs. 35%, p = 0.02) and similar in patients receiving adjuvant radiation therapy (43% vs. 45%, p = 0.30) at 10 years. Debulking of the tumor (hazard ratio [HR] = 6.41, p = 0.01) and a local recurrence (HR = 9.52, p = 0.005) were associated with death due to disease. Complications occurred in 19 (73%) patients, leading to reoperation in 9 (35%) patients; this rate was similar in intralesional and en bloc procedures.ConclusionSurgical resection of mobile spine chordomas is associated with a high rate of complications; however, en bloc resection can provide a hope for cure and appears to confer better oncologic outcomes for these tumors without an increase in complications compared to lesser resections.

Abstract: Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer in the United States with more than 2.5 million treated annually. Genetic studies have revealed that approximately 90% of BCCs have a mutation in the hedgehog-signaling pathway. Patients with BCC usually have an excellent prognosis with surgical modalities, however, patients with locally advanced BCC may potentially experience significant cosmetic or functional impairment, with only surgical intervention. Vismodegib is a hedgehog pathway inhibitor that has been successful in treating patients with locally advanced BCC. We report a patient with BCC with a good response to vismodegib and a novel xanthomatous change in the excision specimen.

Abstract Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72–0.86)]; >0–<5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

431 Background: Patients (pts) with localized PC do not routinely undergo comprehensive genomic profiling (CGP) unless they develop recurrent or metastatic disease. KRAS is the most frequently mutated gene in PC, however, the impact of different KRAS mutations in localized PC has not been well characterized. We interrogated our genomic database to analyze the KRAS status in PC pts who presented with localized disease at diagnosis (Dx). Methods: We identified PC pts at our institution who underwent CGP utilizing the Foundation One CDx assay and had localized disease at initial Dx; these pts were categorized into resectable/borderline resectable PC (LPC) and locally advanced PC (LAPC). All pts with LPC and LAPC underwent neoadjuvant chemotherapy and chemoradiation prior to possible surgery (all intended therapy - AIT). Tissue from metastatic sites was used for CGP in pts who developed recurrent/metastatic disease before or after completion of AIT. The primary tumor was used for CGP in pts who completed AIT without subsequent relapse or in the absence of adequate metastatic tissue. Effect of each gene on response and survival outcomes was estimated using proportional odds and Cox regression analysis, respectively, adjusting for stage. Results: 75 pts were identified, median age at Dx was 65 years, 59% were male, 65% had a primary tumor in the pancreatic head. 38 (86%) pts with LPC completed AIT compared to 21 (68%) pts with LAPC (p<0.001). KRAS mutation was detected in 95% (71/75) of pts– 94% (67/71) in codon 12 and 6% (4/71) in codon 61. The various KRAS mutations and their association with completion of AIT is summarized in the table. The likelihood of completing AIT did not differ based on KRAS wildtype (WT) vs mutated status (p =1.00), the mutated codon (codon 12 vs. codon 61; p =1.00) or the individual KRAS point mutations (p = 0.7); however, all patients with G12A (N= 1), G12C (N=1), G12L (N=1) and G12R (N=11) mutations completed AIT. KRAS status (mutated vs. WT) and the individual KRAS mutations were not associated with overall survival (OS) after adjusting for stage (p= 0.13 and p = 0.26 respectively). Median OS for patients with LPC and LAPC, was 39 months (mos) and 29 mos respectively. Conclusions: KRAS status and individual KRAS mutations did not have an impact on completing AIT or mOS; however, these findings need to be interpreted with caution due to the inherent biases involved in such analyses. The clinical significance and functional relevance of KRAS G12A, G12C, G12L and G12R mutations, though relatively rare, needs further characterization as well as mechanistic elucidation. [Table: see text]

Objectives/HypothesisThe purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality.Study DesignDelphi method‐based survey series.MethodsA multidisciplinary, multi‐institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work‐up.ResultsThe international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18).ConclusionThis consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best‐practice applications of systemic bevacizumab for patients with early‐onset or less‐severe disease phenotypes.Level of Evidence5 Laryngoscope, 131:E1941–E1949, 2021

Background: Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA), and perioperative antibiotics are commonly administered to try to mitigate the chance of infection. Intraosseous regional administration (IORA) of prophylactic antibiotics during TKA is a method of antibiotic delivery that has been shown to achieve markedly higher tissue concentrations at much lower doses. Other advantages include ease of administration, ability to time the antibiotic delivery with the surgical start time for maximal effectiveness, and less systemic side effects. The concept is similar to a Bier block, except that IORA involves the use of antibiotics instead of local anesthetic to perfuse the limb and is given via intraosseous rather than intravenous access. Description: After standard patient preparation and draping, the tourniquet is inflated and an intraosseous needle is inserted into the proximal medial face of the tibia, just medial and slightly above the level of the tubercle. A large syringe containing the desired antibiotic (typically 500 mg vancomycin suspended in normal saline solution) is connected to the needle and the solution is administered over 1 to 2 minutes. The intraosseous needle can then be removed and the surgical procedure proceeds as it normally would per surgeon preference and technique. Alternatives: Systemic administration of intravenous antibiotics, vancomycin powder, and antibiotic-impregnated cement are alternative options that can be utilized during TKA. Rationale: IORA has several distinct advantages over other methods of antibiotic delivery, including the ability to (1) deliver antibiotic directly to the surgical bed and avoid systemic delivery, (2) precisely time and quickly administer antibiotics to achieve highest concentrations at the start of and throughout the surgical procedure, and (3) avoid several common and potentially serious side effects, especially those associated with antibiotics such as vancomycin. Expected Outcomes: This technique for antibiotic delivery achieves markedly higher tissue concentrations compared with systemic administration, without prolonged preoperative infusion times. Intraosseous delivery optimizes timing and reduces the risk of systemic side effects while simultaneously providing equal or enhanced antibiotic prophylaxis in TKA. This delivery mechanism is especially useful in patients who are at high risk for infection and in the revision TKA setting. Further, there is little to no additional risk and the use of this method does not substantially prolong operative time. Important Tips: The proximal aspect of the tibia is the optimal injection site because the cortex is thinner in this region, making needle insertion easier. Additionally, the metaphyseal bone allows faster flow rates for the infusion. We have found that insertions made slightly more proximally are easier and have faster flow rates. Of note, although the antibiotic is infused into the tibia, as seen in the attached technique video, intraosseous administration achieves rapid uptake into the vascular tree. Therefore, all tissues distal to the tourniquet, including the femur and patella, will receive this optimal dose as well. We prefer the use of a power driver (EZ-IO; Teleflex); however, manual needles (Cook Medical) can also be utilized. Longer needles are available if needed for obese patients. Flow rates are variable and the infusion typically takes 1 to 2 minutes to complete. If the flow rate is slow, twisting and withdrawing the needle slightly (2 to 4 mm) may increase the rate. This contrasts with the 1 to 2-hour intravenous infusion time required when vancomycin is administered systemically. In our experience, intraosseous injection is still successful in the case of a previous high tibial osteotomy, although the flow rate may be slower. In complex revision cases with compromised proximal tibial bone, the medial malleolus is an alternative site for intraosseous administration. Choice of antibiotic: as vancomycin is difficult to adequately administer intravenously, it is ideally suited for IORA. We have studied and utilized a 500-mg dose of vancomycin suspended in a solution of 140 mL of normal saline solution (prepared by our pharmacy). Of note, we have not found rapid infusion of intraosseous vancomycin to cause red-man syndrome as it would with rapid systemic infusion. This is because of the lower dose of 500 mg and the use of the tourniquet, which keeps the antibiotic in the local tissues about the knee without allowing systemic exposure. All patients, regardless of weight or the size of their limb, receive the dose of 500 mg of vancomycin. As cefazolin does not have the same difficulties with intravenous administration, we continue to use standard intravenous prophylaxis with an appropriate weight-based dose of cefazolin prior to incision. Indications for IORA of vancomycin include clinical scenarios in which vancomycin would be administered intravenously. These indications include revision TKA, obesity (body mass index >40 kg/m 2 ), diabetes, beta-lactam allergy, known colonization with methicillin-resistant Staphylococcus aureus (MRSA) , patients coming from institutions with a high prevalence of MRSA , previous ligamentous surgical procedure or osteotomies, and current or recent smokers. IORA can be utilized even in the primary TKA setting if the patient is considered high-risk as defined by the criteria above. We also use IORA during reimplantation following 2-stage exchange for PJI and in patients undergoing irrigation and debridement for acute PJI when the organism has been identified preoperatively.

Abstract BACKGROUND The prognostic importance of maximal resection of contrast enhancing and non-contrast enhancing disease has been established. Nonetheless, glioblastomas exist within the framework of complex neural circuitry serving cognition, movement, and behavior consequential leading to neurological impairments. The prognostic importance of neurological impairments on survival remains poorly understood. METHODS This is a retrospective, single cohort study from UCSF including 316 eligible patients diagnosed over 20 years with 9.6 years of follow-up. All patients underwent surgical resection for newly diagnosed glioblastoma for whom survival, molecular, preoperative and postoperative MRI images, and clinical data were available. All patients had chemoradiation treated IDH-wild-type glioblastoma with available preoperative and 1-month post-surgical resection neurological outcomes. We employed survival models and recursive partitioning (RPA) to investigate multivariate relationships of overall survival (OS). RESULTS Preoperative neurological impairments were present in 75.6% (n= 239) and new post resection impairments were identified in 37.3% (n=117). Univariate analysis confirmed that new postoperative cognitive impairment [HR 7.91, 95% CI 2.47-25.33] and hemiplegia [HR 3.38, 95% CI 0.83-13.67] (not hemiparesis) impact OS. Risk stratified grouping by RPA demonstrated that gross total resection of contrast enhancing tumor in patients with no new postoperative neurological impairments confers the longest OS (median OS 27.1 months 95%CI 21.5-33.7). Patients with any residual tumor volume after surgery but no new neurological deficits experience a similar survival to younger patients (under 65) with 1 or more new postoperative neurological deficits (median OS 16.6 months 95%CI 15.2-19.2). Shortest OS is identified in patients with any volume of residual tumor plus 1 or more new postoperative neurological deficits and age over 65 (median OS 11.4 months, 95%CI 9.3-13.5). CONCLUSIONS This study confirms that new postoperative neurological impairments impact overall survival in patients with chemoradiation treated IDH-wild-type glioblastoma.