March 2023

This prospective cohort study examined the predictors of recurrent appendicitis after non-operative management to find that despite high proportion of complicated appendicitis in general, presence of an appendicolith was the most reliable predictor of a patient developing recurrent appendicitis within 6 months. 

Summary: In this study released in March of this year in the American Journal of Surgery, the researchers prospectively analyzed acute appendicitis patients treated at a tertiary care center who received non-operative management (NOM) to identify predictors of recurrence. While other studies have examined predictors of failure of NOM (appendicolith, duration of symptoms, appendiceal diameter, and elevated temperature), few have looked at predictors of recurrent appendicitis in patients after successful NOM. This topic is important to practicing general surgeons, as the utility of interval appendectomy remains a topic of debate. 

This was a prospective cohort study of patients who received treatment for appendicitis at Vancouver General Hospital between May 2019 and April 2021. The primary outcome was recurrent appendicitis within 6 months after discharge from the index appendicitis episode. Patients with both complicated and uncomplicated appendicitis were included. Patients who failed NOM and received an appendectomy during their initial admission were excluded. 

Of the 699 patients who presented with appendicitis during the study period, 80 (11%) were initially treated non-operatively, of which 6 patients required a same-admission appendectomy, leaving 74 patients in the cohort (median age 33, 47% women). Most of the patients (n=45, 65%) had complicated appendicitis, and 20% (n=15) had an appendicolith. A minority of patients (n=12, 16%) required drainage. Twenty-one patients (29%) had recurrent appendicitis within 6 months, with a median time to recurrence of 17 days. Most patients who recurred (71%) were managed operatively. The recurrence rate was 67% in patients who had an appendicolith, and 38% in those without. On univariate and multivariate analyses, presence of an appendicolith was the only factor associated with a significantly higher risk for recurrent appendicitis. 

In a recent follow-up of the CODA trial, presence of an appendicolith was associated with a 30-day rate of appendectomy, although the researchers were unable to distinguish why the appendectomies were performed (e.g., persistent symptoms, surgeon preference, or recurrence). One of the strengths of this study is that the researchers used symptomatic recurrence as their primary endpoint. However, as a single-center study its generalizability is limited. Regardless, presence of an appendicolith can be utilized by providers in tailoring their decision-making and counseling patients on the need for an interval appendectomy. 

This resource paper in Cell Metabolism from renowned Harvard collaborators describes a simple method for exploring extracellular fluid in tissues and tumors that is easily accessible to surgeons looking to dig further into the protein secretome of surgical samples. 

Synopsis: Nearly every discipline from sepsis to cancer has focused on identifying novel secreted proteins that could provide insight into disease mechanism. In particular, there is great interest in identifying novel secreted proteins that can serve as biomarkers to non-invasively speak to disease diagnosis and progression. Unfortunately, characterizing secreted proteins is notoriously difficult as they are often lost in tissue processing, overlooked due to their dynamic range of concentration in blood, or missed due to lack of coverage for low abundance protein.

This work from Bruce Spiegleman and Edward Couchani at Harvard builds upon prior publications in gynecological cancer to present a simple approach to looking for potentially secreted proteins not in the blood or tissue, but in the in between – in extracellular fluid or spaces between the cells. Here they combine proteomics methodologies with a straightforward tissue processing technique (read: conducive to OR tissue samples) to perform in-depth proteomic profiling of the fat and muscle. Briefly, the extracellular fluid was isolated through low-speed centrifugation over a 20um mesh filter and then immunodepleted of albumin and immunoglobulin that might otherwise muddy the protein LC-MS signals. 

The authors used this method to reliably detect changes in the extracellular fluid from the muscle and fat of mice after exercise and cold-exposure, respectively, and identified a novel role for the protein, prosaposin, to act as a secreted factor. Prosaposin is the precursor to saposin, a glycoprotein involved in lysosomal degradation known for involvement in Gaucher’s Disease. Prosaposin had been previously described in the blood and CSF with increased stress, but little more was known about why and how this protein was secreted. The author’s further investigate prosaposin with genetic overexpression models and propose that the protein is a secreted factor, potentially from the muscle, that promotes mitochondrial function in the fat. 

The great strength of this resource paper is the simple method they validate to explore a new biological compartment – a method that is particularly relevent to surgeons looking to further explore protein changes in surgical specimens. For example, when applied to tumors or tissues from various disease states, this approach may open the door to identifying new biomarkers and mechanisms. Limitations include that their method may still potentially lose proteins with their albumin/IGG clean up and does not account for proteins secreted in extracellular vesicles, however, this methodology will likely be further optimized by this group and others to address these issues and customize the approach for a wide-variety of future biological questions.

This paper detailing the longer-term outcomes from the PRESERVE trial found that IVC filters were safe and effective in preventing PE’s in the setting of a known DVT when anticoagulation had failed or was not possible; but there remains an emphasis on patient follow up and making a plan for retrieval. 

Summary: Current guidelines recommend Inferior Vena Cava Filter  (IVCF) placement for patient with an acute pulmonary embolism (PE) or deep venous thrombosis (DVT) with a contraindication to anticoagulation. Approximately 65,000 IVCF are placed in the United States annually with only 35% eventually being retrieved. The PRESERVE study – Predicting Safety and Efficacy of Inferior Vena Cava filters – aimed to characterize the current practice patterns of IVCF placement including the indications and safety of placement and use over time, along with frequency and success of IVCF retrieval.

This study was a multicenter, prospective, non-randomized trial that enrolled patients from 54 sites across the country between 2015 and 2019. 1421 patients were enrolled and evaluated at time of the procedure; participants were followed every 3-6 months for 2 years after placement as well as one month after IVCF retrieval. The primary safety end points examined included freedom from serious adverse events (perforation, IVCF embolization, caval occlusion, or new DVT) within the first 12 months of placement. Primary effectiveness end points were procedure success and freedom from new clinically significant PE within 12 months of placement and 1-month post retrieval.  

The majority of patients enrolled in this trial had an infrarenal, retrievable IVCF placed. 72.2% of patients had a filter placed because of contraindication to anticoagulation; 9.4% because of failure of medical therapy, and 8.9% placed for prophylaxis. 89% of participants reached the primary safety end point and 96% reached the primary effectiveness end point. Only 30 (<2%) participants reported procedural adverse events (including suboptimal positioning of the filter). Two patients experienced access related complications. New or worsened PE occurred in seven patients in the perioperative period, all of whom had acute venous thromboembolism (VTE) at presentation. Embolization of a filter or struct of a filter occurred in four patients. 93 (6.5%) of patients experienced recurrent VTE or caval occlusion within an average of 60 days from filter placement. None of the events were fatal. At 12 month follow-up, out of 211 available CT scans, 31 patients (15.4%) were found to have strut perforation greater than 5mm, but only 3 of these were considered clinically significant. 634 patients underwent filter retrieval with over a 96% successful retrieval rate. There was one reported death from innominate vein injury during retrieval.

This study found that adverse events during and after IVCF placement were rare. However; less than 45% of patients ended up having their retrievable filter removed. The authors suggest best practices include a plan should be made for removing the filter by the physician placing it, with frequent reevaluation for potential removal in timely intervals. They also highlighted the potential for penetration and involvement with surrounding structures when there is perforation greater than 5mm of the struts of the filter and should lead to prompt evaluation for filter removal. Overall, the PRESERVE study continues to demonstrate that IVC filters are safe and effective against preventing PE when utilized appropriately.