Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.

The Surgical Clerkship in the COVID Era: A Natural Language Processing and Thematic Analysis.

INTRODUCTION: Responses to COVID-19 within medical education prompted significant changes to the surgical clerkship. We analyzed the changes in medical student end of course feedback before and after the COVID-19 outbreak. METHODS: Postclerkship surveys from 2017 to 2022 were analyzed including both Likert scale data and free text, excluding the COVID outbreak year 2019-2020. Likert scale questions were compared between pre-COVID (2017-2019) and COVID-era cohorts (2020-2022) with the Mann-Whitney U-test. Free-text comments were analyzed using both thematic analysis and natural language processing including sentiment, word and phrase frequency, and topic modeling. RESULTS: Of the 483 medical students surveyed from 2017 to 2022, 297 responded (61% response rate) to the included end of clerkship surveys. Most medical students rated the clerkship above average or excellent with no significant difference between the pre-COVID and COVID-era cohorts (70.4% Versus 64.8%, P = 0.35). Perception of grading expectations did significantly differ, 51% of pre-COVID students reported clerkship grading standards were almost always clear compared to 27.5% of COVID-era students (P = 0.01). Pre-COVID cohorts more frequently mentioned learning and feedback while COVID-era cohorts more frequently mentioned case, attending, and expectation. Natural language processing topic modeling and formal thematic analysis identified similar themes: team, time, autonomy, and expectations. CONCLUSIONS: COVID-19 presented many challenges to undergraduate medical education. Despite many changes, there was no significant difference in clerkship satisfaction ratings. Unexpectedly, the greater freedom and autonomy of asynchronous lectures and choice of cases became a highlight of the new curriculum. Future research should investigate if there are similar associations nationally with a multi-institutional study.

Roles, Responsibilities, and Expectations of Medical Students on Surgical Subinternships: A Modified Delphi Consensus Study.

PURPOSE: Surgical subinternships are important rotations for students preparing for a career in general surgery; however, these rotations often vary by institution and service. This modified Delphi study was conducted to reach a consensus set of roles, responsibilities, and expectations of fourth-year medical students on their surgical subinternships. METHOD: Candidate statements on roles, responsibilities, and expectations of subinterns were categorized into 7 domains: rotation structure, rounding and patient care, operating room conduct, technical skills, knowledge base, clinic, and professionalism. Expert panels were assembled of key stakeholders: program directors, clerkship directors, other education faculty, trainees, and recent subinterns. Three Delphi rounds were conducted from January to April 2023 to reach consensus defined a priori as a Cronbach α ≥ 0.8 and 80% or greater panel agreement. RESULTS: Forty-six expert panelists were recruited to participate in Delphi rounds, with 100%, 95.7%, and 97.8% response rates in the first, second, and third rounds, respectively. By the third round, 67 statements reached consensus as essential roles, responsibilities, and expectations of surgical subinterns. Key themes from these 67 statements included subinterns approximating the role of an intern with respect to work hours, patient care responsibilities, basic technical skills, and knowledge base. Panelists rated rounding and patient care as the most important domain, followed closely by professionalism. Additional key domains for evaluation in descending order were knowledge base, operating room conduct, clinic, and technical skills. By the third round, notable disagreements in the Delphi process included technical skills and rounding and patient care (93.3% and 88.9% agreement, respectively). CONCLUSIONS: This study provides a national consensus on core roles, responsibilities, and expectations for medical students completing surgical subinternships. Students can use these recommendations to prepare for subinternships, whereas faculty as well as residents and fellows can use them to evaluate applicants for general surgery residency positions.

Simple versus radical cholecystectomy and survival for pathologic stage T1B gallbladder cancer.

BACKGROUND: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer. METHODS: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018. Patients were stratified by surgical management. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Altogether, 950 patients were identified with pathologic T1B gallbladder cancer: 187 (19.7 %) receiving simple and 763 (80.3 %) radical cholecystectomy. Median OS was 89.5 (95 % CI 62.5-137) and 91.4 (95 % CI 75.9-112) months for simple and radical cholecystectomy, respectively (log-rank p = 0.55). Receipt of simple cholecystectomy was not associated with greater hazard of mortality compared to radical cholecystectomy (HR 1.23, 95 % CI 0.95-1.59, p = 0.12). DISCUSSION: In this analysis, we report comparable outcomes with simple cholecystectomy among patients with pathologic T1B gallbladder cancer. These findings suggest that highly selected patients, such as those with R0 resection and imaging at low risk for residual disease and/or nodal metastasis, may not benefit from extended resection; however, radical cholecystectomy remains standard of care until prospective validation can be achieved.

Longitudinal Integrated Clerkships and Undergraduate Surgical Education: A Scoping Review and Gap Analysis.

OBJECTIVE: Longitudinal integrated clerkships (LICs) are an increasingly popular approach to medical student clinical education, and the literature describing them is expanding. Despite this, there is a lack of understanding for how surgery didactics and skills are currently taught as a part of the LIC curriculum. DESIGN: We conducted a scoping literature review in July 2022 using terms related to LIC and surgical education. Abstract and full-length text screening followed. Data extraction was completed in August 2022. Articles published in English, focused on LIC students, and discussed any element of LIC curriculum surgical education was included. SETTING: Scoping literature review. PARTICIPANTS: A total of 282 studies describing LICs were identified from the scoping literature review. After applying inclusion and exclusion criteria, 37 (13%) studies describing some element of surgical education were included. RESULTS: Of these 37 studies, the majority did not delve into pertinent details related to students' surgery experience, expectations, and surgical skills accomplishments. Four studies (11%) reported on the outpatient surgical experience, such as minimum required time that students were expected to be in the clinic, and 8 studies (22%) described the inpatient and operating room exposure. Only 1 study (3%) described the surgical floor management of surgical patients, including tasks like documentation and wound care, and 3 studies (8%) reported formal assessment of surgical skills, such as suturing technique. CONCLUSIONS: Our study highlights the paucity LIC literature examining the relationship between this curricular innovation and the unique needs of medical students on a surgical clerkship. Surgeon educators should embrace the opportunity to contribute LIC curriculum development and subsequent investigation into how this modality interfaces with the learning objectives of undergraduate surgical education. A formal description of essential curriculum components for all surgical LIC programs is needed to ensure appropriate surgical education across the varied LIC models.

Impact of primary tumor resection and metastasectomy among gastroentero-pancreatic neuroendocrine tumors with liver metastases only on survival.

BACKGROUND: Despite recommendations for primary tumor resection (PTR) with or without liver resection (LR) in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and isolated liver metastases, there are conflicting data for their impact on overall survival (OS). METHODS: 2320 patients with GEP-NETs and isolated liver metastases were identified from NCDB. Multiple imputations were used to accommodate missing data, and inverse probability of treatment weighting (IPTW) was conducted to minimize bias. RESULTS: Patients with PTR had a greater OS than those without PTR (3-year rate of 88.6% vs. 69.9%, P < 0.001), which was preserved in the adjusted analysis (IPTW-adjusted HR = 0.387, 95% CI: 0.264-0.567; P < 0.001). Patients with LR had a greater OS than those without LR (3-year rate 87.7% vs. 75.2%, P = 0.003), which was also preserved in adjusted analysis (IPTW-adjusted HR = 0.450, 95% CI: 0.229-0.885; P = 0.021). Patients undergoing both PTR and LR had the greatest survival advantage than those with other surgical interventions (P < 0.001). CONCLUSIONS: Either PTR or LR is associated with improved survival for GEP-NET patients with isolated liver metastases. However, there remains significant selection bias in the current study, and caution should be exercised when selecting patients for resection.

Who Benefits? An Assessment of Resident Benefits at Top 50 Academic Institutions.

OBJECTIVE: Residency serves as a crucial time in the professional and personal development of young physicians. Extensive effort is devoted to the clinical training of residents across the country. However, many residents report concerns with compensation, quality of life, and benefits during their clinical training. We sought to evaluate the benefits packages of resident physicians in comparison with other full-time employees at their institutions. SETTING: "Top 50" Residency programs in Medicine, Surgery, and Pediatrics in the United States. DESIGN: To accomplish this task we selected the, "Top-50," institutions for medicine, pediatrics, and surgery using Doximity's Residency Navigator and compared the benefits of residents at these institutions with full-time employees by accessing benefits offerings listed on institutional websites. RESULTS: We found that residents were more likely to receive parking benefits and gym memberships, while full-time employees were more likely to be offered flexible spending accounts, retirement benefits, and tuition support. CONCLUSIONS: Residents receive different benefits packages than their colleagues employed in full time positions at the same institutions. Further discussion regarding the benefits offered to physicians, and the role that benefits play in resident wellbeing is warranted in light of these findings.

Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation.

OBJECTIVES: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA). METHODS: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm. CONCLUSION: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.

Initial Management Strategy and Long-Term Outcomes in 186 Cases of Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a rare but important nonatherosclerotic cause of acute coronary syndrome. Indications for revascularization and long-term outcomes of SCAD remain areas of active investigation. We report our experience with initial management strategy and long-term outcomes in SCAD. We reviewed all patients treated at our institution from 1996-2021 with a SCAD diagnosis. Demographics, comorbidities, clinical presentations, angiography findings, and management strategies were obtained by chart review. The primary outcome was a composite of cardiac death, recurrent/progressive SCAD, subsequent diagnosis of congestive heart failure, or subsequent/repeat revascularization after the initial management. Unadjusted Kaplan-Meier survival analysis was performed. Of 186 patients with a SCAD diagnosis treated at our institution, 149 (80%) were female. Medical management was the initial treatment in 134 (72.0%) patients, percutaneous coronary intervention (PCI) in 43 (23.1%), and coronary artery bypass grafting in 9 (4.8%). Surgery/PCI intervention was associated with younger age (38.8 vs 47.7 years, P = 0.01), ST elevation myocardial infarction on presentation (67.0% vs 34.0%, P < 0.001), lower ejection fraction (45.0% vs 55.0%, P = 0.002), and left anterior descending coronary artery dissection (75.0% vs 51.0%, P = 0.006). Ten-year freedom from our composite outcome was similar between revascularized patients and those managed with medical therapy (P = 0.36). Median follow-up time was 4.5 years. SCAD in the setting of ST elevation myocardial infarction, left anterior descending coronary artery involvement, or decreased cardiac function suggests greater ischemic insult and was associated with initial percutaneous or surgical revascularization. Despite worse disease on initial presentation, long-term outcomes of patients undergoing revascularization are similar to medically managed patients with SCAD.

Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Background: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment in patients with intraductal papillary mucinous neoplasm (IPMN), a precursor lesion to PDAC, change during disease progression has not been defined. Here we functionally profiled the peripheral immune system and characterized the tumor microenvironment of patients with both IPMN and PDAC. We also tested if sera from patients with IPMN and PDAC functionally reprogram monocytes relative to that of healthy donors. Methods: Pancreatic tissue and peripheral blood were collected at the time of resection from 16 patients with IPMN and 32 patients with PDAC. Peripheral blood and pancreatic tissue/tumor were immunophenotyped using flow cytometry. Whole blood was plated and incubated with R848 (a TLR 7/8 agonist) or LPS (a TLR4 agonist) for 6 hours and TNF expression in monocytes was measured by flow cytometry to measure monocyte activation. To test if TLR sensitivity is determined by factors in patient sera, we preconditioned healthy donor monocytes in serum from PDAC (n=23), IPMN (n=15), or age-matched healthy donors (n=10) followed by in vitro stimulation with R848 or LPS and multiplex cytokine measurements in the supernatant. Results: TNF expression in R848-stimulated peripheral blood monocytes was higher in patients with low grade vs high grade IPMN (65% vs 32%, p = 0.03) and stage 1 vs stage 2/3 PDAC (58% vs 42%, p = 0.03), this was not observed after LPS stimulation. TLR activation correlated with increasing grade of dysplasia from low grade IPMN to high grade IPMN. Serum from patients with IPMN and PDAC recapitulated suppression of TNF induction after R848 stimulation in naïve, healthy donor monocytes. Conclusion: Peripheral blood monocyte TNF secretion inversely correlates with the degree of dysplasia in IPMN and cancer stage in PDAC, suggesting innate immune reprogramming as IPMNs progress to invasive disease. These effects are, at least in part, mediated by soluble mediators in sera.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Impact of Tumor Size and Management on Survival in Small Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Society guidelines remain inconsistent on the role of endoscopic and radiographic surveillance as an alternative to surgical resection of small gastric gastrointestinal stromal tumors (GISTs). Herein, we aimed to assess survival among patients with gastric GISTs undergoing observation versus surgical resection, stratified by tumor size. METHODS: The National Cancer Database (NCDB) was queried for gastric GISTs < 2 cm diagnosed from 2010-2017. Patients were stratified by management strategy-observation vs surgical resection. The primary outcome, overall survival (OS), was examined with Kaplan-Meier and multivariable Cox proportional hazard methods. Subgroup analyses were conducted on tumors < 1 cm and 1-2 cm in size. RESULTS: Altogether, 1208 patients were identified: 439 (36.3%) undergoing observation and 769 (63.7%) receiving surgical resection. In the overall cohort, patients undergoing surgical resection demonstrated improved survival (93.6 vs. 88.8% 5-year OS, p=0.02). In multivariable analysis, upfront surgical resection was not associated with a reduction in mortality; however, there was a significant interaction with tumor size. For patients with tumors < 1 cm, there was no difference in survival based on management strategy. However, resection of tumors 1-2 cm was associated with improved survival relative to surveillance. CONCLUSIONS: While surgical resection and surveillance were associated with similar survival for patients with gastric GISTs < 1 cm, this NCDB analysis suggests that patients with tumor size ≥ 1 cm may benefit from upfront surgical resection. Prospective studies comparing these two approaches and their impact on recurrence-free and disease-specific survival are needed to better align consensus guidelines and recommendations.

Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry. PATIENTS AND METHODS: Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]. CONCLUSION: Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.