September 2023

This nonrandomized controlled trial presents the long-term data of the Oslo group’s pilot trials in Liver Transplant for unresectable Colorectal liver metastases from 2006-2020. With a total n=61 with median disease free survival (DFS) of 11.8 mo, overall survival (OS) of 60.3 mo, and survival after relapse of 37.1 mo. Notably, they characterized negative predictors of overall survival which included large tumor size, progressive disease on chemo, high CEA value, large number of lesions as well as several others.  These findings suggest that appropriately selected patients have comparable long-term survival to those receiving a liver transplant for conventional indications.

Summary: 
Colorectal Cancer (CRC) is one of the most common malignancies in western countries, with many patients having synchronous or metachronous metastases. The liver Is a primary source of metastasis, however only ~20% of patients are candidates for liver resection with a 5-year overall survival (OS) between 20-30%. Most patients receive palliative chemotherapy which has a 5-year OS of ~10%.

Liver transplant (LT) is most recently being re-explored as a viable option for patients with CRC liver metastases (CRLM) after previously being abandoned due to poor long-term survival in the 1990s. The Oslo group’s pilot studies in LT for CRLM (SECA-1/SECA-2) demonstrated 5-year OS of 60%. The current study presents the long-term data and prognostic factors for these studies from 2006-2020.

During the study period, 72 patients were listed for LT, and 61 pts underwent transplant. Of those transplanted, median DFS was 11.8 mo, with 5-year OS of 50.4%. At the extremes, 1 patient died of complications 1.4 months after transplant while the patient with the longest survival is alive 165 mo after LT. In terms of relapse, 78.3% had relapse after LT, with median time to relapse of 9 mo. 94% of relapses occurred within 2 years with the latest occurring at 46.4 months. Median OS after relapse is 37.1 mo with 5-year OS of 34.8%.

The Oslo Score (from SECA-1, validated in SECA-2), ranges from 0-4 based on CEA level >80 μg/L, progressive disease while on chemo, largest lesion >= 5.5cm and time from resection of primary tumor to LT <2 yrs. When stratifying by the Oslo score, there were significant differences in OS and 5-year across groups.

These findings show that with appropriate risk stratification (Oslo 0-1), LT for CRLM can have comparable long-term survival to LT for conventional indications. Notably, while recurrence is common, there was still significant survival time after recurrence with additional goal-directed treatment options. 

Limitations of the study include: non-randomized study design, and lack of specific comparator group (conventional LT group). 

Bottom line: LT for CRLM for carefully selected patients can have favorable long-term survival comparable to that of those receiving LT for conventional indications. With improving ability to risk stratify patients, LT for CRLM is increasingly becoming a feasible therapeutic treatment option for patients with CRLMs.  While organ availability continues to be a barrier, we should anticipate an increase in LT for CRLMs in the future.

This article is a review of the local usage of tranexamic acid for its antifibrinolytic effects in soft-tissue procedures. The authors conclude that topical and local administration is safe and effective in reducing operative blood loss, though higher-level evidence is warranted.  

Summary: Tranexamic acid (TXA) is increasingly being utilized in reconstructive and cosmetic procedures for several reasons: to minimize bleeding, obviate the need for blood transfusions, and improve surgical outcomes. It mechanistically acts as a lysine analog, preventing the activation of plasminogen to plasmin. This article comprehensively reviews the literature reported on local delivery of TXA, its effectiveness, and offers recommendations for its utility in plastic surgery. 

The review compiled results from 14 randomized controlled, which included 1923 patients.  These trials were categorized as either superficial tissue, inner organ, or craniomaxillofacial surgery and all RCTs used either local or application of TXA in the soft-tissue. Overall, within each category of surgery, reduction in post-operative bleeding with the use of TXA was reported to range between 20-40%. Modes of delivery of TXA included TXA moistened gauze placed directly over the wound, diluted TXA solution poured into a cavity, irrigation of undiluted TXA solution into a space, or direct tissue infiltration. Addition of TXA to tumescent solution for rhytidectomies, liposuction, and hair transplantation reliably reduced hematoma rates, closed-suction drain output, and ecchymosis. Post-operative hematoma requiring intervention was consistently higher in placebo groups or non-TXA patient cohorts. RCTs involving open surgery of internal organs found topical application of TXA resulted in both reduction in bleeding volumes as well as transfusion rates. Similarly, among minimally invasive procedures supplementing irrigation fluid with TXA, there was a comparable 24-38% decrease in blood loss. 

Topical application is subjectively reported to achieve superior hemostatic effect as it penetrates the raw wound surface. However, the authors acknowledge topical delivery is not always feasible, particularly near the central nervous system. No difference was noted among incidence of systemic adverse effects when comparing topical to systemic delivery modalities. 

Some potential secondary benefits of TXA administration are discussed, including reduction in post-operative inflammatory processes and improved healing in fractures. Among other specialties, TXA has demonstrated utility in preventing leakage at colonic anastomotic sites, erythematous or melasma spurs in dermatology, and fewer intra-abdominal adhesions. 

Limitations of this study include the inherently small sampling of RCTs, comparison of different types of surgeries with different bleeding risks, variable definitions for blood loss, and variability among TXA application techniques. 

Bottom line: Topical or locally infiltrated tranexamic acid is a viable adjunct to assist with operative blood loss, posing a minimal risk profile of systemic adverse effects. Superior drug delivery mechanisms and optimal dosing patterns have yet to be determined.

This retrospective study investigated the future success of NIH F32 funded surgical residents compared to internal medicine residents. The authors found a total of 269 F32 funded surgical residents and 735 F32 funded internal medicine residents between the years of 1992 and 2021. They then showed that F32 funded internal medicine residents were five times more likely to obtain a K award and twice as likely to obtain an R01 compared to surgical residents. 

Summary:
Residents have several funding mechanisms available when perusing dedicated research time. The NIH Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship (F32) is a 1-to-3-year award that provides structured mentorship and an education plan to provide trainees with biomedical education for future research endeavors. This is sometimes considered the first step to obtain a future K award and ultimately an R01. Previous studies have shown a significant drop in K and R01 funded surgeons compared to other medical specialties prompting the authors to investigate outcomes of F32 funded surgical residents compared to internal medicine residents. 

The authors collected information from all F32 grant recipients holding an MD or equivalent degree in a Department of Surgery or Department of Medicine from 1992-2021. The Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database was used to obtain this data. Ultimately, they found 269 F32 awarded surgical residents and 735 F32 awarded internal medicine residents. It is important to note that almost all the internal medicine residents were awarded their F32 during fellowship when they had dedicated research time. 

The authors showed that F32 funded surgical residents were more likely to be male (77.3% vs 62.4%, P<0.0001), hold a department chair (2.6% vs 0.5%, P=0.005) or division chief (7.8% vs 2.2%, P<0.0001) position but less likely to have a graduate degree (17.5% vs 34.7%, P<0.0001) compared to internal medicine residents. Cardiothoracic surgery (34.6%), vascular surgery (12.3%) and pediatric surgery (7.4%) had the highest number of trainees for surgical F32s. Pulmonology and critical care (38.4%), cardiology (18.6%) and nephrology (15.8%) had the highest number of F32 internal medicine awardees. 

Next, the authors compared subsequent NIH grants for F32 funded surgical vs internal medicine residents. Of the surgical F32 funded residents 18 (7.5%) were able to obtain a K award compared to 274 (37.3%) of the internal medicine residents (P<0.0001). 24 (10%) surgical F32 residents obtained an R01 compared to 145 (19.7%) F32 funded internal medicine residents (P<0.0001). 

These results demonstrate that surgical trainees who start on the NIH funded path through the F32 mechanism are less likely to obtain future NIH funding compared to internal medicine residents. One important limitation of this study is that it does not consider other funding mechanisms such as T32 grants, societal grants, or foundation grants. The paper does highlight the challenges facing surgical residents who wish to obtain future funding NIH grant funding mechanisms. 

Bottomline:
The F32 NIH fellowship is an important first step to obtaining future NIH funding, but surgical residents awarded this funding mechanism are less likely to obtain K awards or an R01 compared to F32 funded internal medicine residents.

This is a prospective randomized control trial (RCT) of 502 patients comparing laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) for patients with locally advanced gastric cancer that require D2 lymph node dissections. The authors found that at 5 years, LADG with D2 lymph node dissection was noninferior to ODG when comparing relapse-free survival, overall survival, and safety.

Summary: This prospective RCT included 502 patients with locally advanced gastric cancer who required distal gastrectomy with D2 lymph node dissection across 37 institutes in Japan between November 2009 and July 2016. Patients were randomized to either the LADG (n=252) or the ODG group (n = 255). The primary study end point was 5-year relapse-free survival (RFS) after surgery, and secondary end points were 5-year overall survival (OS) and safety. 

The 5-year RFS was 73.9% in the ODG group and 75.7% in the LADG group (p=0.03 for noninferiority). The 5-year OS was 79.8% in the ODG group and 81.7% in the LADG group (p=0.34). After curative resection, recurrence occurred in 18.1% of the ODG group and 17.7% of the LADG group.  Subgroup analyses of 5-year RFS were also done based on sex (male or female), age (<65 vs >= 65 years), BMI (<= 20 vs 20-25 vs >25), clinical stage, clinical depth of invasion, clinical N category, pathological stage, pathological T category, and pathological N category. There were no significant differences in between 5-year RFS across these subgroups. The LADG group was associated with longer operating time (median: 291 minutes) as compared to the ODG group (205 minutes; p <.001) and lower estimated blood loss (median: 30 mL LADG, 141 mL ODG). There was no statistically significant difference between reoperation, readmission, or 30-day and in-hospital mortality rates. No patients in the LADG group required conversion to open surgery from intraoperative complications. 

The results of this study show that LADG is comparable to ODG in regards to 5-year RFS and 5-year OS, and is favorable in regards to post-operative recovery with decreased blood loss. In this study, rates of pancreatic fistula formation in the LADG group were low (despite previous RCTs showing high frequency of fistula formation after LADG), and patients with metastatic node-positive cancer had better survival rates in the LADG group than the ODG group. 

Limitations of this study include excluding patients whose BMI was greater than 30 which contributes to the difficulty with generalizing study data to Western countries (it is estimated that >40% of adults in the United States have a BMI >30). D2 lymphadenectomies are also less frequently done in the United States given the lower incidence of gastric cancer as compared to Eastern Asia. Additionally, specific qualification criteria related to laparoscopic skills was required for surgeons operating on the LADG group, highlighting the importance of laparoscopic qualifications in performing surgery but possibly serving as a limiting factor in scalability in real-life practices. 

Bottom line: Laparoscopy-assisted distal gastrectomy for patients with locally advanced gastric cancer requiring D2 dissection is non-inferior to open distal gastrectomy in regard to 5-year relapse-free survival, 5-year overall survival, and safety.