March 2024

This prospective phase 2 study evaluated the use a programmed death 1 (PD-1) inhibitor for patients with mismatch-repair gene deficient, locally advanced rectal cancer. This interim analysis showed that all patients treated with the PD-1 inhibitor at six months have had a complete clinical response to this therapy.

Summary: Total neoadjuvant therapy is the current standard of care treatment for locally advanced rectal cancer in the United States. This consists of systemic chemotherapy either before or after chemo-sensitizing radiation, all of which are administered prior to surgical resection. Although effective, this treatment approach is associated with significant toxicities, including bowel, bladder and sexual dysfunction. Because of this, there is increased interest in the implementation of organ-sparing, non-operative management for the ~20-25% of patients who develop a complete clinical response following completion of total neoadjuvant therapy. Around 5-10% of rectal cancers are deficient in mismatch-repair genes (dMMR). Prior studies have shown that dMMR colorectal cancers respond poorly to the standard chemotherapy regimens used to treat locally advanced rectal cancer; however, metastatic dMMR rectal cancers have improved treatment responses to programmed death 1 (PD-1) immune checkpoint blockade. This trial sought to evaluate the treatment response of locally advanced rectal cancer to neoadjuvant single agent PD-1 blockade.

Adult patients with dMMR locally advanced rectal cancer were administered PD-1 blockade for 6 months. Patients who developed a complete clinical response to this treatment were continued on a watch and wait surveillance pathway. Those who did not develop a complete clinical response would receive standard chemoradiotherapy followed by surgery. The primary endpoint of the current reported data was overall treatment response to PD-1 blockade. This trial is still ongoing, with additional endpoints to be reported as data is accrued.

Sixteen patients have been enrolled at the time of this interim analysis, 12 of which completed 6 months of PD-1 blockade. All 12 patients who completed the 6 months of treatment developed a complete clinical response, and as such none of these 12 patients have received chemoradiotherapy or surgery. Specifically, no evidence of tumor has been seen for any of these 12 patients on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. Median follow-up time among these 12 patients has been 12 months.

This trial has provided very promising results, although a number of questions remain unanswered. Twenty to 30% of patients who have a clinical complete response after chemotherapy and radiation therapy develop a local recurrence. Additionally, in a major trial evaluating treatment responses of metastatic colorectal cancer to PD-1 blockade (KEYNOTE-177), only 55% of patients were reported to be alive without cancer progression at 12 months, and only 70% had an ongoing response at 3 years. Long term data regarding recurrence following complete clinical response from neoadjuvant PD-1 blockade is not known given the short follow-up time reported thus far. Nevertheless, these promising results may represent the beginning of a paradigm shift in the treatment of dMMR locally advanced rectal cancer.

Bottom line: Mismatch repair–deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade in short time follow up. Long-term follow up and analysis is needed to determine efficacy and safety of this regimen for locally advanced rectal cancer.

This randomized, single-center clinical trial evaluated the efficacy of probe-based near-infrared autofluorescence (NIRAF) technology in aiding the identification of abnormal parathyroid glands during parathyroidectomy. The authors found that NIRAF significantly improved the identification of parathyroid glands and reduced the need for frozen section analysis. 

Summary: Primary hyperparathyroidism (pHPT) is a common endocrine disorder, typically successfully treated with parathyroidectomy. However, about 2-10% of the time, even experienced surgeon may fail to localize all the diseased/hyperfunctional parathyroid glands (PGs). Preoperative imaging modalities are often insufficient to localized PGs, leading to reliance on surgeon experience. In the past few years, near-infrared autofluorescence (NIRAF) technology has shown promise in aiding in PG identification and thus, this study aimed to assess the impact of probe-based NIRAF on parathyroid identification as well as other operative factors. 

This trial was conducted between 2020 and 2022 at a single center, recruiting patients 18 years of age and older from two surgeons’ clinic – one senior surgeon (>20 years' experience) and one junior surgeon (<5 years' experience). Patients were either undergoing surgery for pHPT or persistent/recurrent pHPT after failed prior procedure, which were diagnosed using serum calcium and parathyroid hormone (PTH). All patients had to have at least an ultrasound for preoperative localization preoperatively. Patients were assigned to either the experimental arm (probed based NIRAF) or the control arm (no probe based NIRAF). The primary outcomes were rate of persistent pHPT, number of glands identified, operative time, need for frozen section analysis, and rate of permanent hypoparathyroidism. 

Overall, 160 patients were enrolled in the trial, with 80 in each arm. Significantly more PGs were identified with high confidence in the NIRAF cohort (244 PGs, 3.1 PGs per patient) as compared with the control cohort (214 PGs, 2.7 PGs per patient) (p=0.04). After performing multivariate analysis to account for intersurgeon variation and procedure variability, the number of PGs identified with high confidence was improved with the use of probe-based NIRAF (adjusted odds ratio=4.25; 2.5%–97.5% CI: 2.21–8.52, P<0.001). Additionally, the use of NIRAF reduced the number of FS analyses performed intraoperatively. However, NIRAF did not impact clinical outcomes such as persistent hyperparathyroidism, hypoparathyroidism, or operative time. 

The performance accuracy of the probe was validated across 244 PGs and 56 nonparathyroid tissues—thyroid nodules, fatty tissues, lymph nodes, thymic tissues—in the experimental NIRAF cohort of 80 patients, The device yielded 98.8% sensitivity, 67.9% specificity, and an overall 93.0% accuracy (κ =0.74), with a positive predictive value of 93.1% and negative predictive value of 92.7%. The sources for false-positive measurements in nonparathyroid tissues were predominantly brown fat, thymic tissues, and thyroid nodules, occurring in 18 out of 56 nonparathyroid tissues, leading to a false-positive rate of 32.1%.

Limitations of this study include the fact that it was performed at a single institution, which may affect generalizability. Additionally, the sample size is quite small and not appropriately powered to detect small differences in some of the rare outcomes, such as persistent HPT or hypoparathyroidism. Lastly, over half of the cohort did not have more than 6 months of follow up, and thus, long term operative success and failure is unable to be evaluated. 

Bottom line: Probe-based NIRAF technology shows promise as an intraoperative tool for improving the identification of parathyroid glands during parathyroidectomy. 

This retrospective cohort study looks at the trends and outcomes of robotic surgery for emergency general surgery cases. They found there has been an increase in use of robotics, with small decreases in length of stay and less chance of conversion to an open procedure as compared to laparoscopic surgery.  

Summary: In this retrospective cohort study from JAMA surgery, the authors evaluate the use of robotics in emergency general surgery (EGS) cases, evaluating both temporal trends and outcomes, when compared to laparoscopic surgery. The authors used the PINC AI Healthcare Database (PHD) between 2013 and 2021 to identify patients who underwent the following urgent or emergent EGS cases: cholecystectomy, colectomy, inguinal hernia repair (IHR), or ventral hernia repair (VHR). Those cases were chosen because they are among the most common EGS procedures that can utilize a robotic approach in the elective setting. The primary outcome of the study was the temporal trend in use of the robotic surgical approach. Secondary outcomes, analyzed using propensity score-matching, included conversion to open surgery and hospital length of stay (LOS). 

Of the 1,067,263 patients identified, 75% (n=793,800) underwent a cholecystectomy, 8% a colectomy (n=89,098), 6% an IHR (n=65,039), and 11% a VHR (119,326). The use of robotic surgery increased for all procedures between 2013 and 2021; 2.5-8.8% for cholecystectomy, 1.4-8,8% for colectomy, 0.4-15.3% from IHR, and 0.7-9.6% for VHR. Patients receiving robotic surgery were more likely to be overweight or obese compared to those receiving laparoscopic surgery. Using propensity-score matching to balance the two cohorts, robotic surgery was found to be associated with a significantly lower risk of conversion to open surgery compared with laparoscopic surgery for all EGS procedures. Additionally, robotic surgery was associated with a decrease in post-operative LOS for colectomy (6.44 vs. 6.91 days, p<0.001), IHR (1.56 vs. 1.76 days, p<0.001), and VHR (2.38-2.54 days, p=0.002). 

The results of this study are not particularly surprising; it is expected that the use of robotic surgery in EGS procedures would increase, as robotic trained surgeons and by proxy, robotic surgeries, have increased overall in recent years. Additionally, as robotic surgery has been shown to be particularly useful in overweight patients, predictably, patients receiving robotic surgery were more likely to be overweight and obese. While the authors found a decrease in LOS of patients undergoing robotic surgery, the results lack clinical significance, as the largest difference in length of stay between robotic and laparoscopic surgery was less that 0.5 days; however, this could be beneficial from a cost or the healthcare system perspective. Overall, this study does provide fodder for thought and a direction for future studies. 

There are several limitations of this study, including the inability to distinguish urgent from emergency cases/procedures, which inevitably is an important qualifier when considering access to the robot or ability to use robotics. It is not unreasonable to assume that a general surgeon will have less difficulty booking an urgent case robotically (where there is a luxury of time and availability of the robotic), as compared to an emergent case (where they may run into difficulty finding an available robot or finding appropriately trained robotic operating room staff). Therefore, as the robot becomes even more prevalent, future studies should investigate its utility in true emergent EGS cases. 

Bottom line: Robotic surgery is being increasingly utilized in general surgery. This could have positive implications at both the patient level and the health system level.