Analgesic efficacy of surgeon placed paravertebral catheters compared with thoracic epidural analgesia after Ivor Lewis esophagectomy: a retrospective non-inferiority study.

Background: The Ivor Lewis esophagectomy is an operation that involves a laparotomy and a right thoracotomy, both of which are associated with severe postoperative pain and subsequent impairment of respiratory function. Currently, the accepted "gold standard" for postoperative analgesia for laparotomies and thoracotomies is the thoracic epidural. A systematic review has shown paravertebral blocks to be equivalent to epidural analgesia for post-thoracotomy pain control and have decreased incidence of nausea and vomiting, hypotension and respiratory depression. To our knowledge, the use of the paravertebral catheter (PVC) in open Ivor Lewis esophagectomy has not been formally studied. The primary outcome is the area under the curve (AUC) pain scores in the first 48 hours after surgery. Methods: We performed a retrospective chart review of the open Ivor Lewis esophagectomy patients at our local institution, with local research ethics board (REB) approval. Results: A total of 92 patients were included in this study: 43 patients had a PVC and 49 had a thoracic epidural for postoperative pan control. Overall, the PVC group was non-inferior and statistically equivalent to the epidural group. Time to ambulation in the PVC group was non-inferior compared to epidurals. The PVC group was superior when comparing total opioid consumption. Conclusions: Our retrospective study continues to challenge the role of epidurals as the gold standard of pain control post thoracotomy and laparotomy. Further prospective studies with a larger population are needed to better compare the two modalities.

Multicentre positive deviance seminar to generate best practice recommendations to reduce anastomotic leak and length of stay for patients undergoing oesophagectomy.

BACKGROUND: We describe a novel process using positive deviance (PD) with the Canadian Association of Thoracic Surgeons members, to identify perioperative best practice to minimise anastomotic leak (AL) and length of stay (LOS) following oesophagectomy. To our knowledge, this is the first National combination of level 1 evidence with expert opinion (ie, PD seminar) aimed at reducing AL and LOS in oesophageal surgery. Our primary hypothesis is that a multicentre National PD seminar is feasible, and could lead to the generation of best practices recommendations aimed at reducing AL and LOS in patients with oesophageal cancer. METHODS: Adverse events, LOS and AL incidence/severity following oesophagectomy were prospectively collected from seven Canadian thoracic institutions using Thoracic Morbidity and Mortality classification system (2017-2020). Anonymised display of centre's data were presented, with identification of centres demonstrating PD. Surgeons from PD sites discussed principles of care, culminating in the consensus recommendations, anonymously rated by all (5-point Likert scale). RESULTS: Data from 795 esophagectomies were included, with 25 surgeons participating. Two centres were identified as having the lowest AL rates 44/395 (11.1%) (vs five centres 71/400 (17.8%) (p<0.01)) and shortest LOS 8 days 45 (IQR: 6-14) (vs 10 days (IQR: 8-18) (p<0.001)). Recommendations included preoperative (prehabilitation, smoking cessation, chemotherapy for patients with dysphagia, minimise stents/feeding tubes), intraoperative (narrow gastric conduit, intrathoracic anastomosis, avoid routine jejunostomy, use small diameter closed-suction drains), postoperative day (POD) (early (POD 2-3) enteral feeding initiation, avoid routine barium swallow studies, early removal of tubes/drains (POD 2-3)). All ranked above 80% (4/5) in agreement to implement recommendations into their practice. CONCLUSION: We report the feasibility of a National multicentre PD seminar with the generation of best practice recommendations aimed at reducing AL and LOS following oesophagectomy. Further research is required to demonstrate whether National PD seminars can be an effective quality improvement tool.

Ten-year follow-up of endoscopic mucosal resection versus esophagectomy for esophageal intramucosal adenocarcinoma in the setting of Barrett's esophagus: a Canadian experience.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective treatment for esophageal intramucosal adenocarcinoma (IMC), with similar recurrence and mortality rates versus esophagectomy in up to 5 years of follow-up. Long-term outcomes to 10 years have not been studied. This retrospective study investigates IMC eradication, recurrence, morbidity and mortality at 10 years following EMR versus esophagectomy in a single Canadian institution. METHODS: Patients with IMC treated via esophagectomy or EMR from 2006 to 2015 were included. Post-EMR endoscopic follow-up occurred every 3 months for 1 year, every 6 months for 2 years and every 12 months thereafter. Categorical variables were expressed as percentages and continuous variables as mean with standard deviation or median and interquartile range. The student's t-test and Fischer's exact test were used for comparisons. Survival analysis utilized the Kaplan-Meier estimator and log-rank test. RESULTS: Twenty-four patients were included. Patient and tumor characteristics were similar between groups. Median follow-up for EMR and esophagectomy were 85.2 months [IQR 64.8] and 126 months [IQR 54] respectively. A mean of 1.3 EMR (SD 1.1) were required for eradication, which was seen in 12 patients (12/14, 86%). No EMR-related complications occurred. Disease progression was seen in two patients (2/14, 14%); local recurrence was seen in 1 patient (1/14, 7%). Esophagectomy eradicated IMC in 10 patients (10/10, 100%); recurrence was seen in 2 (2/10, 20%, metastatic). Major, early esophagectomy-related morbidity affected 3 patients (3/10, 30%), and late morbidity was documented for 9 (9/10, 90%). Esophagectomy and EMR had similar recurrence rates (p = 0.554). Esophagectomy was associated with significantly more procedure-related morbidity (p < 0.001). There was no difference in mortality (p = 0.442) or disease-free survival (p = 0.512) between treatment groups. CONCLUSION: EMR and esophagectomy for the treatment of IMC are associated with comparable recurrence rates and disease-free survival in 10-year follow-up. EMR is associated with significantly lower procedure-associated morbidity. EMR can be used to treat T1a distal esophageal adenocarcinoma with minimal procedure-related morbidity, and acceptable oncologic outcomes in long-term follow-up.

Multicentre positive deviance to reduce adverse events and length of stay after pulmonary resection.

BACKGROUND: Postoperative adverse events (AEs) following pulmonary resection enormously impact patient well-being, length of stay (LOS) and healthcare costs. Standardised AE data collection can be used to identify positive outliers demonstrating positive deviance (PD) who may be helpful to inform the best practice. Here, we describe our initial experience of a novel quality improvement process using PD to reduce LOS and AEs. METHODS: AE rates and LOS were collected from four centres (2014-2020) using a common dictionary. Surgeons repeatedly participated in 60 to 90 min seminars consisting of the following process: identify outcome and procedure targeted, review relevant best evidence literature, view all data anonymised by surgeon or centre (if multicentre), choose and reveal identity of best performance PD outliers, who discuss their management principles while all receive self-evaluation reports, followed by collegial discussion to generate consensus recommendations, voted by all. We assessed overall impact on AEs and LOS using aggregate data in a before/after analysis. RESULTS: A total of 131 surgeons (average 12/seminar) participated in 11 PD seminars (8 local and 3 multicentre), yielding 85 consensus recommendation (average 8/seminar). Median LOS following lobectomy decreased from 4.0 to 3.0 days (p=0.04) following local PD seminars and from 4.0 to 3.5 days (p=0.11) following multicentre seminars. Trends for reductions in multiple AE rates were also observed. CONCLUSION: While limited by the longitudinal design, these findings provide preliminary support for this data-driven, collegial and actionable quality improvement process to help standardise and improve patient care, and merits further more rigorous investigation.

Screening Criteria Evaluation for Expansion in Pulmonary Neoplasias (SCREEN).

The SCREEN study investigated screening eligibility and survival outcomes between heavy smokers and light-or-never-smokers with lung cancer to determine whether expanded risk factor analysis is needed to refine screening criteria. SCREEN is a retrospective study of 917 lung cancer patients diagnosed between 2005 and 2018 in Nova Scotia, Canada. Screening eligibility was determined using the National Lung Screening Trial (NSLT) criteria. Mortality risk between heavy smokers and light-or-never-smokers was compared using proportional-hazards models. The median follow-up was 2.9 years. The cohort was comprised of 179 (46.1%) female heavy smokers and 306 (57.8%) female light-or-never-smokers. Light-or-never-smokers were more likely to have a diagnosis of adenocarcinoma [n=378 (71.6%)] compared to heavy smokers [n=234 (60.5%); P< 0.001]. Heavy smokers were more frequently diagnosed with squamous cell carcinoma [n=111 (28.7%)] compared to light-or-never-smokers, [n=100 (18.9%); P< 0.001]. Overall, 36.9% (338) of patients met NLST screening criteria. There was no difference in 5-year survival between light-or-never-smokers and heavy smokers [55.2% (338) vs 58.5% (529); P = 0.408; HR 1.06, 95% CI 0.80-1.40; P = 0.704]. Multivariate analysis showed that males had an increased mortality risk [HR 2.00 (95% CI 1.57-2.54); P< 0.001]. Half of lung cancer patients were missed with the conventional screening criteria. There were more curable, stage 1 tumors among light-or-never-smokers. Smoking status and age alone may be insufficient predictors of lung cancer risk and prognosis. Expanded risk factor analysis is needed to refine lung cancer screening criteria.

Palliative management of a malignant tracheoesophageal fistula using repeat endobronchial laser debridement and esophageal stenting.

A 71-year-old female presented with progressive dysphagia and unexplained weight loss. Computed tomography and esophagogastroduodenoscopy (EGD) revealed invasive esophageal squamous cell carcinoma, which was initially treated with local radiation and esophageal stenting. Over the next year, the patient experienced multiple symptoms and hospital admissions consistent with a malignant tracheoesophageal fistula, despite negative findings on imaging, bronchoscopy, and EGD. Prophylactic antibiotics were initiated based on symptomatology to prevent septic episodes. Stent erosion into the membranous trachea was eventually observed. Neodymium-yttrium-aluminum-garnet laser bronchoscopy was used periodically to debulk the invading tumor around the stent. A percutaneous endoscopic gastrostomy tube was also inserted to facilitate enteral nutrition and avoid aspiration pneumonia. The patient reported significant improvements in respiratory symptoms following each laser debridement and has progressed well beyond the life expectancy associated with malignant tracheoesophageal fistula.

Resection of a Large Growing Mediastinal Germ Cell Tumor Using a Multidisciplinary Approach.

Mediastinal germ cell tumors (GCTs) are rare. Post-chemotherapy residual masses in patients with a nonseminomatous GCT require resection. A patient with a large mediastinal GCT involving the left subclavian artery, superior vena cava (SVC) and hilum of the right lung is presented. Despite a biochemical response to chemotherapy, the tumor enlarged on serial imaging. With guidance from medical oncology, a multidisciplinary surgical team, including cardiac anesthesia, cardiac surgery and thoracic surgery resected the tumor with a staged reconstruction of the SVC. The procedure was well tolerated and yielded clear margins. The final pathology showed a significant associated component of rhabdomyosarcoma.

Pleural solitary fibrous tumour with brain metastasis: an aggressive tumour and pathologic conundrum.

Solitary fibrous tumours of the pleura are a rare finding; those with brain metastases are rarer still. Here, we present the evolution of a pleural solitary fibrous tumour in a 70-year-old male treated surgically, and subsequent brain metastasis requiring emergent craniotomy and excision. The patient received adjuvant radiotherapy to the brain and had no recurrence of brain metastases; however, 1 year surveillance imaging demonstrated metastases to the lungs, liver and spleen for which he received chemotherapy but eventually succumbed to the disease process. Solitary fibrous tumours are most often slow-growing, relatively benign neoplasms. However, up to 10% are malignant. This case highlights the importance of surgical resection of these benign tumours with malignant potential.

Congenital adult tracheoesophageal fistula repair with transthoracic ventilation: a case report.

PURPOSE: To describe our experience using transthoracic ventilation to facilitate oral endotracheal tube (ETT) exchange after accidental ETT cuff rupture during a case of congenital tracheoesophageal fistula (TEF) repair. CLINICAL FEATURES: A 53-yr-old male underwent a congenital H-type TEF repair via right-sided thoracotomy with a single-lumen ETT and a bronchial blocker. A large air leak developed after ETT cuff rupture during fistula closure. Transthoracic intubation via tracheotomy was performed to continue ventilation during an oral ETT exchange in the lateral position. No hypoxia or hemodynamic compromise occurred. CONCLUSIONS: Airway device choice for TEF repair must be carefully considered in conjunction with the surgical team. In the present case of accidental ETT cuff rupture, rescue transthoracic ventilation safely facilitated oral ETT exchange.

RéSUMé: OBJECTIF: Décrire notre expérience avec la ventilation transthoracique pour faciliter l'échange de sonde endotrachéale (SET) orale après la rupture accidentelle du ballonnet de la SET lors d'un cas de réparation d'une fistule trachéo-oesophagienne (FTO) congénitale. CARACTéRISTIQUES CLINIQUES: Un homme de 53 ans a bénéficié d'une réparation de FTO congénitale de type H via une thoracotomie du côté droit avec une SET à simple lumière et un bloqueur bronchique. Une importante fuite d'air est apparue après la rupture du ballonnet de la SET lors de la fermeture de la fistule. Une intubation transthoracique par trachéotomie a été réalisée pour poursuivre la ventilation pendant un échange de SET orale en position latérale. Aucune hypoxie ou trouble hémodynamique ne s'est produit. CONCLUSION: Le choix du dispositif pour voies aériennes pour une réparation de FTO doit être soigneusement examiné en collaboration avec l'équipe chirurgicale. Dans le cas présent d'une rupture accidentelle du ballonnet de la SET, la ventilation transthoracique de secours a facilité un échange de SET orale en toute sécurité.

Large bilateral pulmonary arterial venous malformations treated with embolization and lingulectomy in a patient with hereditary hemorrhagic telangiectasia.

A 76-year-old woman with hereditary hemorrhagic telangiectasia presented to the emergency department with chest pain. Workup revealed multiple bilateral pulmonary arteriovenous malformations (PAVMs) with large aneurysmal venous outflow. A collaborative approach between interventional radiology and thoracic surgery was used in the treatment of these PAVMs.

Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR.

Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options with very low response rate. Lung cancer is the most common cause of cancer death worldwide. Therapies that target driver gene mutations (e.g. EGFR, ALK, ROS1) and checkpoint inhibitors such anti-PD-1 and PD-L1 immunotherapies are being used to treat lung cancer patients. Identification of correlations between driver mutations and PD-L1 expression will allow for the best management of patient treatment. 851 cases of non-small cell lung cancer cases were profiled for the presence of biomarkers EGFR, KRAS, BRAF, and PIK3CA mutations by SNaPshot/sizing genotyping. Immunohistochemistry was used to identify the protein expression of ALK and PD-L1. Total PD-L1 mRNA expression (from unsorted tumor samples) was quantified by RT-qPCR in a sub-group of the cohort to assess its correlation with PD-L1 protein level in tumor cells. Statistical analysis revealed correlations between the presence of the mutations, PD-L1 expression, and the pathological data. Specifically, increased PD-L1 expression was associated with wildtype EGFR and vascular invasion, and total PD-L1 mRNA levels correlated weakly with protein expression on tumor cells. These data provide insights into driver gene mutations and immune checkpoint status in relation to lung cancer subtypes and suggest that RT-qPCR is useful for assessing PD-L1 levels.

Recurrence of primary spontaneous pneumothorax following bullectomy with pleurodesis or pleurectomy: A retrospective analysis.

BACKGROUND: Primary spontaneous pneumothorax is managed initially with observation and chest tube placement, followed by surgical intervention in select cases. With little currently published evidence, the role of surgical pleurodesis or pleurectomy to reduce primary spontaneous pneumothorax recurrence is unclear. This study compares the recurrence rates of primary spontaneous pneumothorax following bullectomy alone versus bullectomy with pleurodesis or pleurectomy. METHODS: A retrospective review was performed at a quaternary hospital for all patients undergoing surgery for primary spontaneous pneumothorax between June 2006 and December 2018. Patient demographics, disease severity, operative technique, and time between initial surgery and recurrence were recorded. Standard statistical techniques were used for univariable and multivariable analyses. RESULTS: Of 222 total included patients, 28 required a second surgery: 4 (1.8%) for prolonged air leak and 24 (10.8%) for recurrent pneumothorax. The median time from first to second surgery was 363 days and 35.7% of recurrences did not present until after two years. Age, sex, smoking, year of initial surgery, disease severity, and surgical technique did not significantly affect recurrence rate on univariable analysis. On multivariable analysis, the odds ratios of recurrence for bullectomy with mechanical pleurodesis or pleurectomy were respectively 0.82 and 0.15 (P=0.218), compared to bullectomy alone. Combined bullectomy, pleurectomy, and pleurodesis was most effective (0/18, 0%). CONCLUSIONS: Bullectomy with pleurectomy and pleurodesis demonstrated a 0% recurrence rate for the treatment of primary spontaneous pneumothorax in this study. Statistical significance was not achieved in univariable or multivariable analyses comparing recurrence rates for the surgical approaches. A multi-center randomized controlled trial with longer follow-up than previously performed is needed to confirm these preliminary findings and optimize surgical management of primary spontaneous pneumothorax.

Tubed Anterolateral Thigh Free Flap for Pharyngoesophageal Reconstruction.

Caustic ingestions can severely injure the upper and lower aerodigestive tract, resulting in detrimental mucosal changes both acutely and chronically. Injuries are most severe following alkaline ingestion. Esophagectomy is often recommended in patients with high-grade esophageal injuries to mitigate the risk of perforation. Esophageal reconstruction after these injuries is often delayed, and staged, allowing adequate tissue stabilization before further manipulation. Here, we report on a 25 year-old woman who presented with a high-grade caustic esophageal injury following the ingestion of an alkaline drain cleaner. She underwent an emergent thoracic esophagectomy, gastrectomy and a cervical salivary esophagostomy. Post-operatively, she developed supraglottic and hypopharyngeal strictures, but maintained a functional larynx. She subsequently underwent a staged, extrathoracic total esophageal reconstruction using an anterolateral thigh (ALT) myocutaneous free flap with laryngeal preservation. Although serial esophageal dilatations and trans-oral laser procedures for pharyngeal strictures were required, she was able to maintain the ability to swallow.

Molecular profiling of non-small cell lung cancer.

Lung cancer is generally treated with conventional therapies, including chemotherapy and radiation. These methods, however, are not specific to cancer cells and instead attack every cell present, including normal cells. Personalized therapies provide more efficient treatment options as they target the individual's genetic makeup. The goal of this study was to identify the frequency of causal genetic mutations across a variety of lung cancer subtypes in the earlier stages. 833 samples of non-small cell lung cancer from 799 patients who received resection of their lung cancer, were selected for molecular analysis of six known mutations, including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK. A SNaPshot assay was used for point mutations and fragment analysis searched for insertions and deletions. ALK was evaluated by IHC +/- FISH. Statistical analysis was performed to determine correlations between molecular and clinical/pathological patient data. None of the tested variants were identified in most (66.15%) of cases. The observed frequencies among the total samples vs. only the adenocarcinoma cases were notable different, with the highest frequency being the KRAS mutation (24.49% vs. 35.55%), followed by EGFR (6.96% vs. 10.23%), PIK3CA (1.20% vs. 0.9%), BRAF (1.08% vs. 1.62%), ALK (0.12% vs. 0.18%), while the lowest was the HER2 mutation (0% for both). The statistical analysis yielded correlations between presence of a mutation with gender, cancer type, vascular invasion and smoking history. The outcome of this study will provide data that helps stratify patient prognosis and supports development of more precise treatments, resulting in improved outcomes for future lung cancer patients.

Forecasting pulmonary air leak duration following lung surgery using transpleural airflow data from a digital pleural drainage device.

BACKGROUND: Prolonged air leak (PAL) is often the limiting factor for hospital discharge after lung surgery. Our goal was to develop a statistical model that reliably predicts pulmonary air leak resolution by applying statistical time series modeling and forecasting techniques to digital drainage data. METHODS: Autoregressive Integrated Moving Average (ARIMA) modeling was used to forecast air leak flow from transplural air flow data. The results from ARIMA were retrospectively internally validated with a group of 100 patients who underwent lung resection between December 2012 and March 2017, for whom digital pleural drainage data was available for analysis and a persistent air leak was the limiting factor for chest tube removal. RESULTS: The ARIMA model correctly identified 82% (82/100) of patients as to whether or not the last chest tube removal was appropriate. The performance characteristics of the model in properly identifying patients whose air leak would resolve and who would therefore be candidates for safe chest tube removal were: sensitivity 80% (95% CI, 69-88%), specificity 88% (95% CI, 68-97%), positive predictive value 95% (95% CI, 86-99%), and negative predictive value 59% (95% CI, 42-79%). The false positive and false negative rate was 12% (95% CI, 12-31%) and 20% (95% CI, 12-31%). CONCLUSIONS: We were able to validate a statistical model that that reliably predicted resolution of pulmonary air leak resolution over a 24-hour period. This information may improve the care of patients with chest tube by optimizing duration of pleural drainage.

Pain management within an enhanced recovery program after thoracic surgery.

Evidence for ERAS within thoracic surgery (ERATS) is building. The key to enabling early recovery and ambulation is ensuring that postoperative pain is well controlled. Surgery on the chest is considered to be one of the most painful of surgical procedures for both open and minimally invasive surgery (MIS) approaches. Increasing use of MIS and improved perioperative care pathways has resulted in shorter length of stay (LOS), requiring patients to achieve optimal pain control earlier and meet discharge criteria sooner, sometimes on the same day as surgery. This requires optimizing pain control earlier in the postoperative recovery phase in order to enable ambulation and a better recovery profile, as well as to minimize the risk for development of chronic persistent postoperative pain (CPPP). This review will focus on the options for pain management protocols within an ERAS program for thoracic surgery patients (ERATS).

Optimal management of postoperative parenchymal air leaks.

Air leaks are the most common complication after pulmonary resection. Enhanced recovery after surgery (ERAS) programs must be designed to manage parenchymal air leaks. ERAS programs should consider two components when creating protocols for air leaks: assessment and management. Accurate assessment of air leaks using traditional analogues devices, newer digital drainage systems, portable devices and chest X-rays (CXR) are reviewed. Published data suggests that digital drainage systems result in a more confident assessment of air leaks. The literature regarding the management of postoperative air leaks, including the number of chest tubes, the role of applied external suction, invasive maneuvers and discharge with a portable device is reviewed. The key findings are that a single chest drain is adequate in the majority of cases to manage an air leak, the use of applied external suction is unlikely to prevent or prolong an air leak, autologous blood patch pleurodesis may potentially shorten postoperative air leaks and there is sufficient data to support that patients can safely be discharged with a portable drainage system. There is also literature to support the design of protocols for management of postoperative air leaks. Standardization of postoperative care through ERAS programs will allow for the design of larger RCTs to better understand some of the controversies around the management of postoperative air leaks.

Digital Air Leak Monitoring for Lung Resection Patients: A Randomized Controlled Clinical Trial.

BACKGROUND: Digital chest drainage devices objectively measure airflow to guide chest tube management. There are contradictory results regarding their utility in reducing length of stay and chest tube duration. The objective of this study was to compare digital and analog devices in patients undergoing anatomic lung resection. METHODS: A single-institution randomized trial was conducted. Patients undergoing anatomic lung resection between November 2013 and July 2016 were randomized to digital or analog devices. Chest tubes were managed using a standardized protocol. Hospital length of stay and chest tube duration were primary outcomes. Chest tube clamping, number of chest roentgenograms, and chest tube reinsertion were secondary outcomes. RESULTS: The study randomized 215 patients, with 107 in the digital group and 108 in the analog group. There was no significant difference in outcomes for length of stay (p = 1), chest tube duration (p = 0.71), number of chest roentgenograms performed (p = 0.78) or need for chest tube reinsertion (p = 0.21). The only significant finding was a higher number of patients who had their chest tubes clamped before removal, with 47% in the analog group and 19% in the digital group (p < 0.0001). CONCLUSIONS: Digital devices did not result in reduced chest tube duration or hospital length of stay. Approximately one half of the patients in the analog group had their chest tubes clamped before removal because of uncertainty in air leak assessment. Digital devices provided objective quantification of air leaks that decreased chest tube clamping.

Synthesis of Modular Brush Polymer-Protein Hybrids Using Diazotransfer and Copper Click Chemistry.

Proteoglycans are important brush-like biomacromolecules, which serve a variety of functions in the human body. While protein-bottlebrush hybrids are promising proteoglycan mimics, many challenges still exist to robustly produce such polymers. In this paper, we report the modular synthesis of protein-brush hybrids containing elastin-like polypeptides (ELP) as model proteins by copper-catalyzed azide-alkyne cycloaddition. We exploit the recently discovered imidazole-1-sulfonyl azide (ISA) in a diazotransfer reaction to introduce an N-terminal azide onto an ELP. Next, we use a click reaction to couple the azido-ELP to an alkyne-terminated amine-rich polymer followed by a second diazotransfer step to produce an azide-rich backbone that serves as a scaffold. Finally, we used a second click reaction to graft alkyne-terminated poly(oligoethylene glycol methacrylate) (POEGMA) bristles to the azide-rich backbone to produce the final protein-bottlebrush hybrid. We demonstrate the effectiveness of this synthetic path at each step through careful characterization with 1H NMR, FTIR, GPC, and diagnostic test reactions on SDS-PAGE. Final reaction products could be consistently obtained for a variety of different molecular weight backbones with final total grafting efficiencies around 70%. The high-yielding reactions employed in this highly modular approach allow for the synthesis of protein-bottlebrush hybrids with different proteins and brush polymers. Additionally, the mild reaction conditions used have the potential to avoid damage to proteins during synthesis.