The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis.

BACKGROUND: Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated. METHODS: For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS). RESULTS: Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021). CONCLUSION: The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC.

Does reusable mean green? Comparison of the environmental impact of reusable operating room bed covers and lift sheets versus single-use.

INTRODUCTION: As hospitals strive to reduce their environmental footprint, there is an ongoing debate over the environmental implications of reusable versus disposable linens in operating rooms (ORs). This research aimed to compare the environmental impact of reusable versus single-use OR bed covers and lift sheets using life cycle assessment (LCA) methodology. METHODS: LCA is an established tool with rigorous methodology that uses science-based processes to measure environmental impact. This study compared the impacts of three independent system scenarios at a single large academic hospital: reusable bed covers with 50 laundry cycles and subsequent landfill disposal (System 1), single-use bed covers with waste landfill disposal (System 2), and single-use bed covers with waste disposal using incineration (System 3). RESULTS: The total carbon footprint of System 1 for 50 uses was 19.83 â€‹kg carbon dioxide equivalents (CO2-eq). System 2 generated 64.99 â€‹kg CO2-eq. For System 3, the total carbon footprint was 108.98 â€‹kg CO2-eq. The raw material extraction for all the material to produce an equivalent 50 single-use OR bed cover kits was tenfold more carbon-intensive than the reusable bed cover. Laundering one reusable OR bed cover 50 times was more carbon intensive (12.12 â€‹kg CO2-eq) than landfill disposal of 50 single-use OR bed covers (2.52 â€‹kg CO2-eq). DISCUSSION: Our analysis demonstrates that one reusable fabric-based OR bed cover laundered 50 times, despite the carbon and water-intensive laundering process, exhibits a markedly lower carbon footprint than its single-use counterparts. The net difference is 45.16 â€‹kg CO2-eq, equivalent to driving 115 miles in an average gasoline-powered passenger vehicle. This stark contrast underscores the efficacy of adopting reusable solutions to mitigate environmental impact within healthcare facilities.

The association of permanent versus absorbable fixation on developing chronic post-herniorrhaphy groin pain in patients undergoing laparoscopic inguinal hernia repair.

INTRODUCTION: Fixation of mesh during minimally invasive inguinal hernia repair is thought to contribute to chronic post-herniorrhaphy groin pain (CGP). In contrast to permanent tacks, absorbable tacks are hypothesized to minimize the likelihood of CGP. This study aimed to compare the rates of CGP after laparoscopic inguinal hernia repair between absorbable versus permanent fixation at maximum follow-up. METHODS: This is a post hoc analysis of a randomized controlled trial in patients undergoing laparoscopic inguinal hernia repair (NCT03835351). All patients were contacted at maximum follow-up after surgery to administer EuraHS quality of life (QoL) surveys. The pain and restriction of activity subdomains of the survey were utilized. The primary outcome was rate of CGP, as defined by a EuraHS QoL pain domain score ≥ 4 measured at ≥ 1 year postoperatively. The secondary outcomes were pain and restriction of activity domain scores and hernia recurrence at maximum follow-up. RESULTS: A total of 338 patients were contacted at a mean follow-up of 28 ± 11 months. 181 patients received permanent tacks and 157 patients received absorbable tacks during their repair. At maximum follow-up, the rates of CGP (27 [15%] vs 28 [18%], P = 0.47), average pain scores (1.78 ± 4.38 vs 2.32 ± 5.40, P = 0.22), restriction of activity scores (1.39 ± 4.32 vs 2.48 ± 7.45, P = 0.18), and the number of patients who reported an inguinal bulge (18 [9.9%] vs 15 [9.5%], P = 0.9) were similar between patients with permanent versus absorbable tacks. On multivariable analysis, there was no significant difference in the odds of CGP between the two groups (OR 1.23, 95% CI [0.60, 2.50]). CONCLUSION: Mesh fixation with permanent tacks does not appear to increase the risk of CGP after laparoscopic inguinal hernia repair when compared to fixation with absorbable tacks. Prospective trials are needed to further evaluate this relationship.

Training Future Surgeon Leaders in Environmental Stewardship: A Review of a Decade of the Health Care Sustainability Fellowship.

OBJECTIVE: Since the inception of Ken Lee Memorial Fellowship (KLMF) in 2013, our institution has achieved 10 years of trainee led sustainability projects. The ability of health care organizations to drive sustainability depends on organizational and human capacity. This qualitative study presents the first decade of sustainability fellows' projects, the challenges associated with implementing them, and the environmental and cost impact of these initiatives. DESIGN, SETTING, PARTICIPANTS: All residents in the General Surgery residency program at the Cleveland Clinic, a quaternary hospital, regardless of postgraduate year (PGY) level, are invited to apply for the KLMF program with a short project proposal. One fellow is selected per year. Each project since the program's inception was reviewed qualitatively, relying on data derived from observation, interview of prior fellows, and supervising staff, and analysis of documentation from the annual fellow presentation and abstract, Grand Rounds recording, and fellowship leadership. RESULTS: A targeted approach by each sustainability fellow is encouraged, with the following action cycle for change implementation throughout the 1-year fellowship: identification and discovery of an issue, collaborative planning of an intervention, implementation of the intervention, and evaluation. Projects range from water and waste reduction to education of surgical staff, with positive implications for environmental stewardship in our hospital. However, multiple barriers to completing, scaling, and maintaining sustainability initiatives remain, as demonstrated by challenges faced by our Ken Lee Fellows. CONCLUSIONS: Our goal is that this intensive educational experience within the framework of a graduate medical education curriculum will ensure future generations of surgeons who are thoughtful leaders in environmental stewardship.

Comparing oncologic and surgical outcomes of robotic and laparoscopic pancreatoduodenectomy in patients with pancreatic cancer: a propensity-matched analysis.

INTRODUCTION: Minimally invasive Pancreatoduodenectomy (MIPD), or the Whipple procedure, is increasingly utilized. No study has compared laparoscopic (LPD) and robotic (RPD) approaches, and the impact of the learning curve on oncologic, technical, and post-operative outcomes remains relatively understudied. METHODS: The National Cancer Database was queried for patients undergoing LPD or RPD from 2010 to 2020 with a diagnosis of pancreatic cancer. Outcomes were compared between approaches using propensity-score matching (PSM); the impact of annual center-level volume of MIPD was also assessed by dividing volume into quartiles. RESULTS: A total of 3,342 patients were included. Most (n = 2,716, 81.3%) underwent LPD versus RPD (n = 626, 18.7%). There was a high rate (20.2%, n = 719) of positive margins. Mean length-of-stay (LOS) was 10.4 ± 8.9 days. Thirty-day mortality was 2.8% (n = 92) and ninety-day mortality was 5.7% (n = 189). PSM matched 625 pairs of patients receiving LPD or RPD. After PSM, there was no differences between groups based on age, sex, race, CCI, T-stage, neoadjuvant chemo/radiotherapy, or type of PD. After PSM, there was a higher rate of conversion to open (HR = 0.68, 95%CI = 0.50-0.92)., but there was no difference in LOS (HR = 1.00, 95%CI = 0.92-1.11), 30-day readmission (HR = 1.08, 95% CI = 0.68-1.71), 30-day (HR = 0.78, 95% CI = 0.39-1.56) or 90-day mortality (HR = 0.70, 95% CI = 0.42-1.16), ability to receive adjuvant therapy (HR = 1.15, 95% CI = 0.92-1.44), nodal harvest (HR = 1.01, 95%CI = 0.94-1.09) or positive margins (HR = 1.19, 95% CI = 0.89-1.59). Centers in lower quartiles of annual volume of MIPD demonstrated reduced nodal harvest (p = 0.005) and a higher rate of conversion to open (p = 0.038). Higher-volume centers had a shorter LOS (p = 0.012), higher rate of initiation of adjuvant therapy (p = 0.042), and, most strikingly, a reduction in 90-day mortality (p = 0.033). CONCLUSION: LPD and RPD have similar surgical and oncologic outcomes, with a lower rate of conversion to open in the robotic cohort. The robotic technique does not appear to eliminate the "learning curve", with higher volume centers demonstrating improved outcomes, especially seen at minimum annual volume of 5 cases.

Impact of neoadjuvant therapy on nodal harvest in clinical stage III rectal cancer: Establishing optimum cut-offs by disease response.

INTRODUCTION: A minimum lymph node harvest (LNH) of 12 is the current standard for appropriate nodal staging in resectable rectal cancer. However, the rise of neoadjuvant chemoradiation (NCRT) and total neoadjuvant therapy (TNT) has been associated with decreasing number of LNH. We hypothesize that as tumor response to neoadjuvant therapy increases, the optimum for LNH to achieve appropriate nodal staging should decrease. METHODS: Patients with clinical stage III rectal adenocarcinoma who underwent NCRT/TNT followed by resection were identified from the National Cancer Database. A JoinPoint regression analysis was used to determine the LNH for each tumor regression grade (TRG) category beyond which the rate of positive nodes does not significantly change. RESULTS: Thirteen thousand four hundred and twenty-six patients met inclusion criteria. Of these, 2406 (17.9%) achieved TRG 0 or ypT0 and 8210 (61.2%) achieved ypN0. Collectively, 2043 patients (15.2%) were reported to have a pathologic complete response (ypT0 ypN0). Positive pathologic nodes were found in 15%, 23%, 31%, 54%, and 53% as ypT stage increased from ypT0 to ypT4, respectively. Similarly, ypN+ rates were 15%, 36%, 41%, and 55% in TRG 0-3. No JoinPoint was identified for TRG 0, whereas inflection points were found at 6-10 nodes for TRG1 (p = 0.002) and TRG 2 (p = 0.016), and at 11-15 nodes for TRG 3. CONCLUSION: The benchmark of retrieving 12 nodes in resectable stage III rectal cancer is not consistently achieved after NCRT/TNT. We demonstrate that the LNH requirement to establish accurate pathologic nodal staging can vary depending on the tumor response to neoadjuvant therapies.

Neoadjuvant Gastric Score: How Response to Neoadjuvant Chemotherapy Affects Overall Survival and Adjuvant Benefit.

INTRODUCTION: The Neoadjuvant Rectal score (NAR) was developed as a short-term surrogate for 5-year overall survival (OS) prediction in locally advanced rectal cancer on the basis of response to neoadjuvant therapy. We aim to assess whether this score can be repurposed for locally advanced gastric adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection. METHODS: Patients with gastric adenocarcinoma treated with neoadjuvant systemic therapy followed by surgical resection were extracted from the National Cancer Database. Neoadjuvant Gastric (NAG) scores were calculated, and patients were stratified into low-, intermediate-, and high-score categories, with low scores predicting longer survival. Patients were propensity-matched 1:1:1 between the groups for OS comparison. We also matched patients within each group 1:1 per receipt of adjuvant therapy and compared 5-year OS. RESULTS: There were 2,970 patients identified. NAG classified patients into low- (n = 396, 13.3%), intermediate-(n = 756, 25.5%), and high (n = 1818, 61.2%) groups. After propensity matching, 5-year OS was significantly different between the matched groups (low-NAG 82%, intermediate-NAG 73%, and high-NAG 39%; p < 0.001). NAG score grouping also predicted OS benefit of adjuvant therapy; low- and intermediate-NAG patients had no OS benefit with adjuvant therapy (86% vs. 84%; p = 0.492, and 77% vs. 74%; p = 0.382, respectively), whereas patients with high-NAG score had a 5-year OS benefit with adjuvant therapy (39% vs. 29%; p = 0.024). CONCLUSION: NAR score may be repurposed to generate a prognostic tool in gastric adenocarcinoma to predict 5-year OS and has the potential to guide decision-making regarding allocation of adjuvant therapy. Further studies should prospectively validate these findings to confirm clinical utility.

Comparing Outcomes of Minimally Invasive and Open Hepatectomy for Primary Liver Malignancies in Patients with Low-MELD Cirrhosis.

INTRODUCTION: Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). METHODS: NSQIP hepatectomy database 2014-2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. RESULTS: There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19-0.72)], PHLF (HR 0.36 [0.15-0.86]), collections requiring drainage (HR 0.30 [0.15-0.63]), postoperative transfusion (HR 0.36 [0.21-0.61]), major (HR 0.45 [0.27-0.77]), and overall morbidity (HR 0.44 [0.31-0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45-0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. CONCLUSION: MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.

Reasons for voriconazole prophylaxis discontinuation in allogeneic hematopoietic cell transplant recipients: A real-life paradigm.

We sought to describe the clinical experience of voriconazole as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant recipients (allo-HCTr). This was a single-center retrospective study of adult allo-HCTr (1 January 2014 to 31 December 2016) who received ≥two doses of voriconazole-AFP. Voriconazole-AFP was started on day +7 post-HCT and continued at least through day +60 post-HCT, or longer as clinically indicated. We reviewed the rate, reasons, and risk factors of voriconazole-AFP discontinuation until day-100 post-HCT. A total of 327 patients were included. Voriconazole-AFP was continued for a median of 69 days (mean: 57.9; range 1, 100): for a median of 90 days (mean :84; range 2, 100) in 180/327 (55%) in the standard-of-care (SOC) group and 20 days (mean :25.6 ; range 1, 89; P-value < .001) in 147/327 (45%) patients in the early-discontinuation-group. Early-voriconazole-AFP discontinuation was due to adverse events, drug interactions, insurance coverage, and other reasons in 101/147 (68.7%), 27 (18.4%), 13 (8.8%), and 6 (4.1%) patients, respectively. Early-voriconazole-AFP discontinuation occurred in 73/327 (22.3%) patients due to hepatotoxicity. Important predictors for early-voriconazole-AFP discontinuation included: graft-versus-host disease grade ≥2 (odds ratio [OR]: 1.9, P-value: .02), alanine-aminotransferase ≥75 IU/ml on voriconazole-administration day-14 (OR: 5.6, P-value: .02) and total bilirubin ≥1.3 mg/dl on voriconazole-administration day-7 (OR: 3.0, P-value: .03). There were 13 proven/probable invasive fungal infections by day-180 post-HCT (8/147, 5.4%, and 5/180, 2.8% in the early-discontinuation and SOC-groups, respectively; log-rank:0.13). By day-180 post HCT, 23/147 (15.6%) and 14/180 (7.8%) patients in the early-discontinuation and SOC-groups had died, respectively (log-rank:0.03). Voriconazole-AFP was discontinued in up to 45% of allo-HCTr. Hepatotoxicity during the first 2 weeks post-HCT is a significant predictor of early-voriconazole-AFP discontinuation.

Autophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression.

Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation of autophagy strongly attenuates primary mammary tumor growth, impaired autophagy promotes spontaneous metastasis and enables the outgrowth of disseminated tumor cells into overt macro-metastases. Transcriptomic analysis reveals that autophagy deficiency elicits a subpopulation of otherwise luminal tumor cells exhibiting basal differentiation traits, which is reversed upon preventing accumulation of the autophagy cargo receptor, Neighbor to BRCA1 (NBR1). Furthermore, pharmacological and genetic induction of autophagy suppresses pro-metastatic differentiation and metastatic outgrowth. Analysis of human breast cancer data reveal that autophagy gene expression inversely correlates with pro-metastatic differentiation signatures and predicts overall and distant metastasis-free survival. Overall, these findings highlight autophagy-dependent control of NBR1 as a key determinant of metastatic progression.

An evaluation of the cost-effectiveness of policy navigators to improve access to care for the poor in the Philippines.

OBJECTIVES: Even when health insurance coverage is available, health policies may not be effective at increasing coverage among vulnerable populations. New approaches are needed to improve access to care. We experimentally introduced a novel intervention that uses Policy Navigators to increase health insurance enrollment in a poor population. METHODS: We used data from the Quality Improvement Demonstration Study (QIDS), a randomized experiment taking place at the district level in the Visayas region of the Philippines. In two arms of the study, we compared the effects of introducing Policy Navigators to controls. The Policy Navigators advocated for improved access to care by providing regular system-level expertise directly to the policy-makers, municipal mayors and governors responsible for paying for and enrolling poor households into the health insurance program. Using regression models, we compared levels of enrollment in our intervention versus control sites. We also assessed the cost-effectiveness of marginal increases in enrollment. RESULTS: We found that Policy Navigators improved enrollment in health insurance between 39% and 102% compared to the controls. Policy navigators were cost-effective at 0.86 USD per enrollee. However, supplementary national government campaigns, which were implemented to further increase coverage, attenuated normal enrollment efforts. CONCLUSION: Policy Navigators appear to be effective in improving access to care and their success underscores the importance of local-level strategies for improving enrollment.

A novel method for measuring health care system performance: experience from QIDS in the Philippines.

OBJECTIVES: Measuring and monitoring health system performance is important albeit controversial. Technical, logistic and financial challenges are formidable. We introduced a system of measurement, which we call Q, to measure the quality of hospital clinical performance across a range of facilities. This paper describes how Q was developed, implemented in hospitals in the Philippines and how it compares with typical measures. METHODS: Q consists of measures of clinical performance, patient satisfaction and volume of physician services. We evaluate Q using experimental data from the Quality Improvement Demonstration Study (QIDS), a randomized policy experiment. We determined its responsiveness over time and to changes in structural measures such as staffing and supplies. We also examined the operational costs of implementing Q. RESULTS: Q was sustainable, minimally disruptive and readily grafted into existing routines in 30 hospitals in 10 provinces semi-annually for a period of 2(1/2) years. We found Q to be more responsive to immediate impacts of policy change than standard structural measures. The operational costs totalled USD2133 or USD305 per assessment per site. CONCLUSION: Q appears to be an achievable assessment tool that is a comprehensive and responsive measure of system level quality at a limited cost in resource-poor settings.

Should we have confidence if a physician is accredited? A study of the relative impacts of accreditation and insurance payments on quality of care in the Philippines.

It is unclear whether health provider accreditation ensures or promotes quality of care. Using baseline data from the Quality Improvement Demonstration Study (QIDS) in the Philippines we measured the quality of pediatric care provided by private and public doctors working at the district hospital level in the country's central region. We found that national level accreditation by a national insurance program influences quality of care. However, our data also show that insurance payments have a similar, strong impact on quality of care. These results suggest that accreditation alone may not be sufficient to promote high quality of care. Further improvements may be achieved with properly monitored and well-designed payment or incentive schemes.