Issue #2: August 10th, 2022

“Nothing ever becomes real till it is experienced — Even a proverb is no proverb to you till your Life has illustrated it”.

--John Keats, 1819

HAPPENINGS THIS MONTH:

• Thank you to all who expressed interest in joining The Keats and applied! We will have our team selected by September’s issue. We hope to provide our wonderful readers more research in the future. Stay tuned.

• Check out our new section→Surgeon Spotlight. Discover the brilliant men and women who contributed to today’s modern surgical practice. This month’s surgeon spotlight is Dr. Emil T. Kocher.

• Do you have any surgical research you would like us to showcase? Email us and let us spread the word!

Can continuous cardiac rhythm monitoring beyond hospital discharge enhance atrial fibrillation (AF) detection among cardiac surgical patients?

Postoperative atrial fibrillation (POAF) is a common clinical problem that occurs after cardiac surgery and is associated with adverse outcomes; however, the current literature focuses on POAF incidents that occur during hospitalization. A well-defined study of POAF occurring weeks to months after cardiac surgery and persisting after discharge is lacking. In this randomized clinical trial, the researchers sought to determine if continuous cardiac rhythm monitoring improved the detection of subclinical POAF in post-surgical patients at risk of stroke during the first 30 days after hospital discharge compared with patients who receive the standard care.

2 groups were monitored. The intervention group was placed on continuous cardiac rhythm monitoring with wearable sensors for 30 days after randomization; monitoring was not required in the standard care group (control). The study included 336 randomized patients (163 in the intervention group and 173 in the usual care group). The primary outcome was measured to be the cumulative atrial fibrillation (AF) or atrial flutter (AFL) with a duration of 6 minutes or longer by continuous cardiac rhythm monitoring or by a 12-lead ECG within 30 days of randomization.

POAF lasting at least 6 minutes was detected in 32 patients (19.6%) in the intervention group vs 3 patients (1.7%) in the control group (absolute difference, 17.9%; 95%CI, 11.5%-24.3%; P < 0.001). This finding indicates that using continuous cardiac rhythm monitoring detected significantly more POAF, with a 17.9% increase in the rate at which AF was detected compared to the usual care group during the first 30 days after hospitalization.

In conclusion, the use of continuous cardiac rhythm monitors would improve the detection of subclinical POAF in post-surgical patients with risk factors for stroke. Further studies are needed to examine the long-term risk of POAF beyond 30 days and the differences in major adverse effects such as cardiovascular outcomes, stroke rates, and the safety and efficacy of oral anticoagulation treatment use in these patients.

To exercise or not BEFORE surgery?

Surgical resection currently stands as the curative treatment for colorectal cancer; And yet, about one third of patients who undergo colorectal surgery will have postoperative complications. Studies have found that over 65% of patients with colorectal cancer are over the age of 65. This fact points to a key element which can be addressed in post-operative care: physical function. These patients are at higher risk for complications and could see some future benefit in improving their exercise capacity. The current literature on prehabilitation effect on postoperative complications is inconclusive and has a tendency to focus on low risk patient pools. Berkel et al conducted a prospective, single-blinded randomized clinical trial on colorectal cancer patients to investigate the effects of a preoperative exercise program (“prerehabilitation”) on postoperative complications following colorectal resection. This group was compared to a control group (“usual care”) which underwent the traditional standard of care. The patients were over 60 years old and had a low baseline preoperative aerobic fitness capacity (defined as oxygen uptake at the ventilator anaerobic threshold with cardiopulmonary exercise test; VO2 at the VAT < 11 mL/kg/min). The prerehabilitation group had 3 weeks of supervised 1-hour combined aerobic and strength training exercise sessions for 3 times a week before their surgery. The primary outcome was defined as the number of patients with 1 or more complications 30 days after colorectal resection.

After 3-weeks of community-based exercise prior to colorectal resection, the rates of postoperative complications were significantly reduced in the prerehabilitation group compared to the usual care group (43% vs 72%; p= 0.02). This study yields a strong recommendation for consistent and moderate-level exercise prior to a major abdominal surgery. Similar to how patients are urged to cease smoking at least 4 weeks prior to surgery, it might be of major benefit to encourage patients to exercise at least 3 weeks prior to their surgery also. However, this is heavily dependent on the patient’s ability to exercise. It would be interesting to examine the effect of various types of exercises (e.g., aerobic vs strength; upright vs sitting) and durations (e.g., 30 minutes vs 60 minutes) on reducing postoperative complications. Additionally, since this study was community-based, it required travel for participation. Thus, a consideration should be taken for home-based exercise programs in future studies. Needless to say, exercising does more good than harm, especially prior to a major surgery in patients who are at high risk for postoperative complications.

Neoadjuvant Treatment or Solely Upfront Surgery in Pancreatic Cancer

The diagnosis of pancreatic cancer is grim with a 5-year survival of roughly 10%. Classification of non-metastatic disease is based on the extent of vascular involvement as either resectable, borderline resectable, or locally advanced. For borderline resectable pancreatic cancer, current guidelines recommend neoadjuvant therapy; however, these recommendations come from clinical trials, rather than randomized controlled trials (RCTs). In recent years, more RCTs regarding treatment have occurred. The purpose of this study was to conduct a meta-analysis that only examined RCTs that compared neoadjuvant therapy with upfront surgery in those with resectable or borderline resectable pancreatic cancer. The authors also conducted a subgroup analysis regarding respectability status and the type of neoadjuvant treatment utilized.

The authors performed this meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses. They utilized Embase, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar to search for RCTs that compared neoadjuvant therapy with upfront surgery in those with resectable or borderline resectable cancer. The primary outcome of the study was overall survival expressed as hazards ratio (HR). Resection rate, microscopically complete resection rate (R0), (N0) negative lymph node resection rate, and major surgical complications were secondary outcomes of this study and were expressed as a risk ratio.

After screening 1863 records and reviewing 26 full text articles, 7 of these articles were included in their analysis with a total patient population of 938. It was found that neoadjuvant therapy improved overall survival compared to upfront surgery (HR 0.66, 95% CI 0.52-0.85, P = 0.001), especially in patients with borderline resectable cancer (HR 0.61, 95% CI 0.44-0.85, P = 0.0004). It was noted that none of the studies used adjuvant FOLFIRINOX, and all studies utilized gemcitabine-based therapy in at least one arm. From this, the authors conclude that neoadjuvant therapy compared to upfront surgery alone increases overall survival in those with borderline resectable pancreatic cancer. However, the authors were not able to conclude whether neoadjuvant therapy improves survival in those with resectable cancer.

The First 5 Years of Uterus Transplant in the US

Absolute uterine-factor infertility (AUFI) is a condition characterized by the inability to get pregnant either because of the lack of a uterus or possessing a non-functioning one. It is one of the major causes of female infertility, affecting 1 in 500 women. Many primary care physicians can provide few options when patients are faced with this difficult diagnosis. Many times the options are limited to gestational carriers or adoption. However, in 2016, transplant surgeons provided a revolutionary alternative. The first US uterus transplant was performed at Cleveland Clinic in 2016 with the first live birth (LB) occurring in 2017. Even though the immediate outcome was achieved, little study has been implemented to investigate the overall outcomes. In this cohort study, 5 years of uterus transplant outcome data was collected from 3 major centers and evaluated. The primary outcomes were patient survival, allography survival, and live birth (LB). Successful uterus transplant was measured by having a viable graft at postoperative day 30. Amongst the 33 patients, 21 of the donors (64%) were Live Donors, while 12 (36%) were Deceased Donors.

Based on this study’s definition of an efficacious uterus transplant, 76% in this cohort were successful. With continued follow-up, it was found that 1-year graft survival rate was 74%. In this group, 74% from LD and 75% from DD groups had 1 year graft survival. The proportion of patients who achieved at least 1 LB after a uterus transplant was 58%, and interestingly, 83% of the patients who achieved 1 year survival graft had at least 1 LB. This study validates the potential effectiveness of surgical intervention for the issue of infertility. And yet, one needs to consider several limitations, such as the small patient pool and, most glaringly, the fact that the indication for transplant in most of these women was for Mayer-Rokitansky-Küster-Hauser syndrome (31 out of 33 patients.) This condition is characterized by the failure of the uterus and vagina to develop properly in women who have a normal ovarian function and external genitalia. To fully consider uterus transplant as a possible alternative for patients, future investigations need to be undertaken on a more diverse patient pool. Due to the small sample size, more extensive and detailed design must be implemented if a uterus transplant is ever to be integrated into general practice.

SURGEON SPOTLIGHT OF THE MONTH: WHO IS KOCHER?

Emil Theodor Kocher

1841-1917

In this month’s surgeon spotlight, we feature Dr. Emil Theodor Kocher (1841-1917), the first surgeon to be awarded the Nobel Prize in Physiology or Medicine in 1909. Dr. Kocher was awarded the Nobel Prize for his work in developing the foundations of thyroid surgery and physiology. In addition, Dr. Kocher was a pioneer in the fields of organ transplantation and endocrinology.

The field of surgery was not perceived as a prestigious field of medicine in Kocher’s time. Similar to John Keats’ time, surgery was considered a manual craft and had been considered as separate from the profession of medicine. Surgical skill was only sought after in emergent situations. It was a field associated with exposing oneself to horrors of war, pain and infection. And yet, the Nobel Prize was awarded to a surgeon for the first time in history.

Dr. Kocher developed a technique to safely resect a goiter, an unprecedented feat in surgery that warranted his Nobel Prize in 1909. Through long-term observations of his patients from his operations, he was able to observe the physiological functions of the thyroid by the effects of its absence. Kocher was the first surgeon to implant human thyroid tissue as an attempt to correct the loss of thyroid functions. In the early 1800s, thyroidectomy was one of the most dangerous surgical procedures of his time, with a mortality rate of 75%. It was so dangerous that some hospitals had it banned. Kocher performed 5,000 thyroidectomies and was able to reduce the mortality to 18%. And it was his intense investigation into thyroid anatomy and surgical technique which made him discover that the removal of the thyroid could lead to cretinism.

Kocher made other contributions to the field of medicine outside of his Nobel Prize. He was the first to complete the chart of human dermatomes, published in 1896. He also developed the “Kocher Maneuver,” the dissection of the lateral peritoneal attachment of the duodenum for exposing the retroperitoneal structures over the great vessels. With his achievements, he was recognized as the leader and pioneer of modern surgery. His approach to physiology led to the development of the field of endocrinology and organ transplantation. Rarely has the Nobel Prize been awarded to a surgeon, but his contributions to the field of surgery and medicine as a whole have had a tremendous impact on present day practice. To this day, many medical students, residents, and surgeons will have used the Kocher forceps, one of the most fundamental tools in surgery named after Dr. Kocher as a lasting reminder of his contributions.

Sources:

1. Tröhler U (2010). Emil Theodor Kocher (1841-1917). JLL Bulletin: Commentaries on the history of treatment evaluation (https://www.jameslindlibrary.org/articles/emil-theodor-kocher-1841-1917/)

2. Schlich T. Nobel Prizes for surgeons: In recognition of the surgical healing strategy. International Journal of Surgery. 2007 Apr 1;5(2):129-33. https://doi.org/10.1016/j.ijsu.2006.04.012

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