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Background: Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer., Methods: We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section., Results: Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7)., Conclusion: In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings., (© 2024. Society of Surgical Oncology.)

Background: Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership., Patients and Methods: An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume., Results: The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable., Conclusions: Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population., (© 2024. Society of Surgical Oncology.)

Competing Interests: The authors report no conflicts of interest.

Background: Observational studies have reported strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe an attempt to estimate the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data., Methods: We propose two target trials among persons with diabetes: (1) bariatric operation (vs. no operation) among individuals who have undergone preoperative preparation (lifestyle modifications and screening) and (2) preoperative preparation and a bariatric operation (vs. neither preoperative nor operative component). We emulated both target trials using observational data of US veterans., Results: Comparing bariatric surgery with no surgery (target trial #1; 8,087 individuals), the 7-year cardiovascular risk was 18.0% (95% CI = 6.9, 32.7) in the surgery group and 18.9% (95% CI = 17.7, 20.1) in the no-surgery group (risk difference -0.9, 95% CI = -12.0, 14.0). Comparing preoperative components plus surgery vs. neither (target trial #2; 10,065 individuals), the 7-year cardiovascular risk was 17.4% (95% CI = 13.6, 22.0) in the surgery group and 18.8% (95% CI = 17.8, 19.9) in the no-surgery group (risk difference -1.4, 95% CI = -5.1, 3.2). Body mass index and hemoglobin A1c were reduced with bariatric interventions in both emulations., Conclusions: Within limitations of available observational data, our estimates do not provide evidence that bariatric surgery reduces cardiovascular disease and support equipoise for a randomized trial of bariatric surgery for cardiovascular disease prevention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Comparing different medications is complicated when adherence to these medications differs. We can overcome the adherence issue by assessing effectiveness under sustained use, as in usual causal 'per-protocol' estimands. However, when sustained use is challenging to satisfy in practice, the usefulness of these estimands can be limited. Here we propose a different class of estimands: separable effects for adherence. These estimands compare modified medications, holding fixed a component responsible for non-adherence. Under assumptions about treatment components' mechanisms of effect, a separable effects estimand can quantify the effectiveness of medication initiation strategies on an outcome of interest under the adherence mechanism of one of the medications. These assumptions are amenable to interrogation by subject-matter experts and can be evaluated using causal graphs. We describe an algorithm for constructing causal graphs for separable effects, illustrate how these graphs can be used to reason about assumptions required for identification, and provide semi-parametric weighted estimators., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This study aims to identify the factors influencing colorectal cancer (CRC) screening practices, along with the barriers and facilitators from the perspective of primary care physicians (PCPs) in Ukraine. Considering health care system challenges, including those posed by the ongoing war, this research seeks to inform improvements in CRC screening and outcomes in Ukraine and other low- and middle-income countries (LMICs)., Methods: A survey was designed and distributed electronically to Ukrainian PCPs, focusing on CRC screening practices, beliefs, and barriers. The survey incorporated questions adapted from established cancer screening surveys and frameworks. Complete responses were collected from 740 PCPs. Sample statistics were computed, and population-level perceptions and associations with CRC screening practices were estimated by standardizing responses to national PCP demographics., Results: The majority of respondents were women (91%) and specialized in family medicine (84%). Respondents believed in the effectiveness of colonoscopy for reducing CRC mortality (80%), with 75% of PCPs referring patients for this screening modality. Major barriers identified include inadequate training of PCPs in screening and lack of resources. Respondents reported high utilization of fecal occult blood test and colonoscopy for screening when these tests were said to be available in their practices. Self-reported familiarity with CRC screening guidelines and participation in educational workshops were positively associated with screening referrals., Conclusion: The study highlights the role of access to CRC screening tests and awareness of screening guidelines in enhancing CRC screening practices among Ukrainian PCPs. Addressing training and resource barriers, alongside public health interventions targeting patient-related barriers, is essential. These findings offer valuable insights for LMICs facing similar challenges, emphasizing the need for tailored strategies to improve cancer screening in these health care settings.

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important., Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival., Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021., Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed., Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up., Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Purpose: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality., Methods: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO 2 /FiO 2  ≤ 200 and SpO 2  ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding., Results: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046)., Conclusion: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial., (© 2024. The Author(s).)

Researchers are often interested in estimating the effect of sustained use of a treatment on a health outcome. However, adherence to strict treatment protocols can be challenging for individuals in practice and, when non-adherence is expected, estimates of the effect of sustained use may not be useful for decision making. As an alternative, more relaxed treatment protocols which allow for periods of time off treatment (i.e. grace periods) have been considered in pragmatic randomized trials and observational studies. In this article, we consider the interpretation, identification, and estimation of treatment strategies which include grace periods. We contrast natural grace period strategies which allow individuals the flexibility to take treatment as they would naturally do, with stochastic grace period strategies in which the investigator specifies the distribution of treatment utilization. We estimate the effect of initiation of a thiazide diuretic or an angiotensin-converting enzyme inhibitor in hypertensive individuals under various strategies which include grace periods., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare., (© The Royal Statistical Society 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Many real-life treatments are of limited supply and cannot be provided to all individuals in the population. For example, patients on the liver transplant waiting list usually cannot be assigned a liver transplant immediately at the time they reach highest priority because a suitable organ is not immediately available. In settings with limited supply, investigators are often interested in the effects of treatment strategies in which a limited proportion of patients receive an organ at a given time, that is, treatment regimes satisfying resource constraints. Here, we describe an estimand that allows us to define causal effects of treatment strategies that satisfy resource constraints: incremental propensity score interventions (IPSIs) for limited resources. IPSIs flexibly constrain time-varying resource utilization through proportional scaling of patients' natural propensities for treatment, thereby preserving existing propensity rank ordering compared to the status quo. We derive a simple class of inverse-probability-weighted estimators, and we apply one such estimator to evaluate the effect of restricting or expanding utilization of "increased risk" liver organs to treat patients with end-stage liver disease., (© 2023 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Background: Whether intubation should be initiated early in the clinical course of critically ill patients remains a matter of debate. Results from prior observational studies are difficult to interpret because of avoidable flaws including immortal time bias, inappropriate eligibility criteria, and unrealistic treatment strategies., Research Question: Do treatment strategies that intubate patients early in the critical care admission improve 30-day survival compared with strategies that delay intubation?, Study Design and Methods: We estimated the effect of strategies that require early intubation of critically ill patients compared with those that delay intubation. With data extracted from the Medical Information Mart for Intensive Care-IV database, we emulated three target trials, varying the flexibility of the treatment strategies and the baseline eligibility criteria., Results: Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared with delaying intubation (95% CI, 6.2-7.9). Risk differences were 0.4 (95% CI, -0.1 to 0.9) and -0.9 (95% CI, -2.5 to 0.7) percentage points in subsequent target trial emulations that included more realistic treatment strategies and eligibility criteria., Interpretation: When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared with those that intubate early. Delaying intubation ultimately avoids intubation in most patients., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Despite their pre- and postoperative components, surgical treatment strategies have typically been cast as point interventions in causal inference research. When longitudinal perioperative components affect outcomes of interest, leaving them unspecified or failing to measure adherence to them complicates the interpretation of effect estimates. Inspired by two recent landmark trials that assessed the risk of stroke or death after transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR), the PARTNER 3 trial and the Evolut Low Risk trial, we discuss possible ways that different postoperative therapies in treatment arms and incomplete adherence to those therapies can impact the interpretation of intention-to-treat effect estimates in surgical trials. We argue that surgical treatments are not necessarily point interventions, and make recommendations for improving the design and analysis of trials involving surgical interventions. Central to these recommendations is the need for investigators to specify and report adherence to longitudinal perioperative treatment components., (© 2023. Springer Nature B.V.)

Background: Clinical guidelines recommend adding a second drug for patients with major depressive disorder who have a partial response and switching antidepressants for those who show no response or intolerance. This guidelines-based strategy was compared with other strategies for the management of unresponsive depression., Methods: A total of 1436 individuals experiencing treatment failure with citalopram and still requiring antidepressant therapy were identified in the STAR∗D (Sequenced Treatment Alternatives to Relieve Depression) trial. A (hypothetical) target trial was then designed and emulated. The following strategies for decision making were compared: sequential monotherapy, sequential dual non-selective serotonin reuptake inhibitor therapy (SD), and a guidelines-based strategy. The primary outcome was symptomatic remission defined as a Hamilton Depression Rating Scale score ≤7 or 2 consecutive scores ≤5 on the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated. Secondary outcomes were serious events (hospitalizations, suicide, and mortality). Inverse probability weighting was used to control for possible confounding., Results: A total of 971 patients were eligible for our emulation. Patients initiating SD had the lowest levels of depression at baseline. The estimated 9-month probability of remission was 43.5% for the sequential monotherapy group, 47.6% for the SD group, and 53.2% for the guidelines-based strategy group. Compared with the sequential monotherapy group, the difference in 9-month probability of remission was -4.2% (95% CI, -15.6 to 4.6) for the SD group and -9.7% (-19.3 to 1.9) for the guidelines-based strategy group. The 9-month relative risks of remission were 1.09 (0.90 to 1.38) and 1.22 (0.96 to 1.46), respectively. Results were consistent across sensitivity analyses. The 9-month relative risks of serious events were 0.77 (0.38 to 1.40) and 0.62 (0.33 to 1.00), respectively., Conclusions: Using the guidelines-based strategy was associated with an increased probability of remission and a lower risk of serious adverse events. The potential implications are substantial given the large number of patients experiencing treatment failure to antidepressants., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: In Ukraine, there is no established colorectal cancer screening program. We aimed to project the number of screening colonoscopies needed for implementation of various CRC screening strategies in Ukraine., Methods: We modified a previously developed Markov microsimulation model to reflect the natural history of adenoma and CRC progression among average-risk 50-74-year-olds. We simulated colonoscopies needed for the following screening strategies: no screening, fecal occult blood test yearly, FOBT yearly with flexible sigmoidoscopy every 5 years, FS every 5 years, fecal immunohistochemistry test (FIT) yearly, or colonoscopy every 10 years. Assuming 80% screening adherence, we estimated colonoscopies required at 1 and 5 years depending on the implementation rate. In one-way sensitivity analyses, we varied implementation rate, screening adherence, sensitivity, and specificity., Results: Assuming an 80% screening adherence and complete implementation (100%), besides a no screening strategy, the fewest screening colonoscopies are needed with an FOBT program, requiring on average 6,600 and 26,800 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. The most screening colonoscopies are required with a colonoscopy program, requiring on average 76,600 and 101,000 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. In sensitivity analyses, the biggest driver of number of colonoscopies needed was screening adherence., Conclusions: The number of colonoscopies needed and therefore the potential strain on the healthcare system vary substantially by screening test. These findings can provide valuable information for stakeholders on equipment needs when implementing a national screening program in Ukraine., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Defunctioning loop ileostomies are used commonly, but there are significant morbidities., Objective: This study aimed to describe the morbidity and mortality associated with the formation and closure of defunctioning loop ileostomies., Design: This descriptive study is based on electronic health records and claims data., Settings: This study was conducted at academic and community hospitals in Ontario, Canada., Patients: Adult patients who had a low anterior resection with concurrent defunctioning loop ileostomy from 2002 to 2014 were included., Main Outcome Measures: Outcomes of interest included 30-day major complications, acute kidney injury, transfusion, and deep space infection. The rate of ileostomy reversal and the percentage of permanent ostomies were also collected., Results: The cohort consists of 4658 patients who underwent low anterior resection with concurrent defunctioning loop ileostomy. The 30-day, 90-day, and 1-year mortality rates of these patients were 1.2%, 2.2%, and 5.1%. The rate of reoperation was 5.5%, the rate of hospital readmission was 13.4%, the rate of major complications was 28.5%, the rate of deep organ/space infection requiring percutaneous intervention was 5.2%, and the rate of acute kidney injury requiring hospitalization was 10.4%. Eighty-six percent had their ileostomy reversed, leaving 13.2% with a permanent ostomy. After ileostomy reversal, 30-day and 90-day mortality rates were 0.6% and 0.9%. The rate of major complications was 10.3%, bowel obstruction 7%, ventral hernia 10.5%, deep space infection 1.7%, and repeat operation 2.3%., Limitations: This study is based on electronic health records and claims data and, thus, the accuracy of results depends on the accuracy of data administration' which can be variable across institutions., Conclusions: Morbidity and mortality of defunctioning loop ileostomies are significant. One in 8 patients will have a permanent ostomy. See Video Abstract at http://links.lww.com/DCR/B810 ., Desde La Formacin Hasta El Cierre Agregada Morbilidad Y Mortalidad Asociada Con Las Ileostomas En Asa Derivativa: ANTECEDENTES:Las ileostomías en asa derivativa se utilizan con frecuencia, pero existen morbilidades importantes.OBJETIVO:Describir la morbilidad y mortalidad asociadas con la formación y cierre de ileostomías en asa derivativa.DISEÑO:Estudio descriptivo basado en historias clínicas electrónicas y datos de reclamaciones.ENTORNO CLINICO:Hospitales académicos y comunitarios en Ontario, Canadá.PACIENTES:Pacientes adultos sometidos a resección anterior baja con concurrente ileostomía en asa derivativa de 2002 a 2014.PRINCIPALES MEDIDAS DE VALORACION:Los resultados de interés incluyeron complicaciones mayores a los 30 días, lesión renal aguda, transfusión e infección del espacio profundo. También se recolectó la tasa de reversión de la ileostomía y el porcentaje de ostomías permanentes.RESULTADOS:La cohorte consistió de 4658 pacientes sometidos a resección anterior baja con concurrente ileostomía en asa derivativa. La mortalidad de estos pacientes, a treinta días, 90 días y un año, fue del 1,2%, 2,2% y 5,1%, respectivamente. La tasa de reintervención fue del 5,5%, el reingreso hospitalario fue del 13,4%, la complicación mayor fue del 28,5%, la infección profunda de órganos / espacios que requirieron intervención percutánea fue del 5,2%, y la lesión renal aguda que requirió hospitalización fue del 10,4%. Ochenta y seis por ciento tuvieron reversión de su ileostomía, dejando al 13.2% con una ostomía permanente. Después de la reversión de la ileostomía, la mortalidad a los 30 días y 90 días fue de 0,6% y 0,9%, respectivamente. La tasa de complicaciones mayores fue del 10,3%, obstrucción intestinal del 7%, hernia ventral del 10,5%, infección del espacio profundo del 1,7% y reintervención del 2,3%.LIMITACIONES:El estudio se basa en registros médicos electrónicos y datos de reclamos y, por lo tanto, la precisión de los resultados depende de la precisión en la administración de datos, que pueden variar entre instituciones.CONCLUSIONES:La morbilidad y la mortalidad de las ileostomías en asa derivativa son significativas. Uno de cada 8 pacientes tendrá una ostomía permanente. Consulte Video Resumen en http://links.lww.com/DCR/B810 . (Traducción-Dr. Fidel Ruiz Healy )., (Copyright © The ASCRS 2021.)

Importance: The association of surgeons' and hospitals' operative volumes with postoperative patient outcomes has been studied for decades and holds important policy implications; however, in many volume-outcome analyses, this association is described without the envisioning of a clear intervention, which often introduces unintentional bias. Acting on such results may lead to unintended consequences from policy interventions or patient recommendations., Objective: To specify how (hypothetical) target trials would be designed to estimate the association between postoperative mortality of patients undergoing operations and a range of surgeon and hospital volume conditions and then to emulate these trials by using observational data., Design, Setting, and Participants: This observational data analysis emulated 4 hypothetical target trials of increasing complexity, ranging from a poorly defined trial that would randomly assign participants only to surgeon volume to one that would randomly assign participants to surgeon volume, hospital volume, and specific surgeon and hospital. This population-based cohort study included 9136 Medicare beneficiaries with a first diagnosis of pancreatic malignant neoplasm who did not require neoadjuvant therapy and underwent pancreatectomy between January 1, 2012, and September 30, 2016. Data analysis was performed between September 1, 2019, and October 8, 2021., Exposures: Number of pancreatectomies performed by surgeon and hospital during the prior year., Main Outcomes and Measures: Ninety-day mortality., Results: The analyses included 9136 Medicare beneficiaries treated by 1358 surgeons at 697 hospitals; median age was 73.3 years (IQR, 69.1-78.1 years), and 4642 were men (51%). When trials with poorly defined interventions on surgeon volume were emulated, the estimated 90-day mortality was 7.9% (95% CI, 6.4%-9.4%) for lower-volume surgeons and 5.2% (95% CI, 2.7%-10.9%) for higher-volume surgeons. When trials with better-defined interventions were emulated, the difference was reduced: 7.8% (95% CI, 6.3%-9.3%) for lower-volume surgeons and 7.2% (95% CI, 6.0%-8.7%) for higher-volume surgeons., Conclusions and Relevance: In this cohort study that emulated 4 different target trials with data from Medicare beneficiaries undergoing pancreatectomy, mortality differences across surgical volume levels were attenuated when the interventions were well defined. The application of the hypothetical target trial framework to this specific volume-outcomes scenario revealed the complexities of this research question and the unintentional biases introduced in prior studies, which emulated poorly defined trials whose results are therefore difficult to interpret. The target trial framework may be of value to outcomes researchers asking questions that correspond to well-defined interventions for the real world.

Background: Prior studies assessing colorectal cancer survival have reported better outcomes when operations are performed at high-volume centers. These studies have largely been cross-sectional, making it difficult to interpret their estimates. We aimed to assess the effect of facility volume on survival following proctectomy for rectal cancer., Methods: Using data from the National Cancer Database, we included all patients with complete baseline information who underwent proctectomy for non-metastatic rectal cancer between 2004 and 2016. Facility volume was defined as the number of rectal cancer cases managed at the treating center in the calendar year prior to the patient's surgery. Overall survival estimates were obtained for facility volumes ranging from 10 to 100 cases/year. Follow-up began on the day of surgery and continued until loss to follow-up or death., Results: A total of 52,822 patients were eligible. Patients operated on at hospitals with volumes of 10, 30, and 50 cases/year had similar distributions of grade, clinical stage, and neoadjuvant therapies. 1-, 3-, and 5-year survival all improved with increasing facility volume. One-year survival was 94.0% (95% CI: 93.7, 94.3) for hospitals that performed 10 cases/year, 94.5% (95% CI: 94.2, 94.7) for 30 cases/year, and 94.8% (95% CI: 94.5, 95.0) for 50 cases/year. Five-year survival was 68.9% (95% CI: 68.0, 69.7) for hospitals that performed 10 cases/year, 70.8% (95% CI: 70.1, 71.5) for 30 cases/year, and 72.0% (95% CI: 71.2, 72.8) for 50 cases/year., Conclusions: Treatment at a higher volume facility results in improved survival following proctectomy for rectal cancer, though the small benefits are less profound than previously reported., (© 2021. The Society for Surgery of the Alimentary Tract.)

The number of operations that surgeons have previously performed is associated with their patients' outcomes. However, this association may not be causal, because previous studies have often been cross-sectional and their analyses have not considered time-varying confounding or positivity violations. In this paper, using the example of surgeons who perform coronary artery bypass grafting, we describe (hypothetical) target trials for estimation of the causal effect of the surgeons' operative volumes on patient mortality. We then demonstrate how to emulate these target trials using data from US Medicare claims and provide effect estimates. Our target trial emulations suggest that interventions on physicians' volume of coronary artery bypass grafting operations have little effect on patient mortality. The target trial framework highlights key assumptions and draws attention to areas of bias in previous observational analyses that deviated from their implicit target trials. The principles of the presented methodology may be adapted to other scenarios of substantive interest in health services research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Operative volume has been used as a marker of quality. Research from previous decades has suggested minimum open abdominal aortic aneurysm (AAA) repair volume requirements for surgeons of 9 to 13 open AAA repairs annually and for hospitals of 18 open AAA repairs annually to purportedly achieve acceptable results. Given concerns regarding the decreased frequency of open repairs in the endovascular era, we examined the association of surgeon and hospital volume with the 30- and 90-day mortality in the Vascular Quality Initiative (VQI) registry., Methods: Patients who had undergone elective open AAA repair from 2013 to 2018 were identified in the VQI registry. We performed a cross-sectional evaluation of the association between the average hospital and surgeon volume and 30-day postoperative mortality using a hierarchical Bayesian model. Cross-level interactions were permitted, and random surgeon- and hospital-level intercepts were used to account for clustering. The mortality results were adjusted by standardizing to the observed distribution of relevant covariates in the overall cohort. The outcomes were compared to the Society for Vascular Surgery guidelines recommended criteria of <5% perioperative mortality., Results: A total of 3078 patients had undergone elective open AAA repair by 520 surgeons at 128 hospitals. The 30- and 90-day risks of postoperative mortality were 4.1% (n = 126) and 5.4% (n = 166), respectively. The mean surgeon volume and hospital volume both correlated inversely with the 30-day mortality. Averaged across all patients and hospitals, we found a 96% probability that surgeons who performed an average of four or more repairs per year achieved <5% 30-day mortality. Substantial interplay was present between surgeon volume and hospital volume. For example, at lower volume hospitals performing an average of five repairs annually, <5% 30-day mortality would be expected 69% of the time for surgeons performing an average of three operations annually. In contrast, at higher volume hospitals performing an average of 40 repairs annually, a <5% 30-day mortality would be expected 96% of the time for surgeons performing an average of three operations annually. As hospital volume increased, a diminishing difference occurred in 30-day mortality between lower and higher volume surgeons. Likewise, as surgeon volume increased, a diminishing difference was found in 30-day mortality between the lower and higher volume hospitals., Conclusions: Surgeons and hospitals in the VQI registry achieved mortality outcomes of <5% (Society for Vascular Surgery guidelines), with an average surgeon volume that was substantially lower compared with previous reports. Furthermore, when considering the development of minimal surgeon volume guidelines, it is important to contextualize the outcomes within the hospital volumes., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

There has been a recent increase in enthusiasm for expansion of living donor liver transplantation (LDLT) programmes. Using all adults initially placed on the waiting list in the United States, we estimated the risk of overall mortality under national strategies which differed in their utilization of LDLT. We used a generalization of inverse probability weighting which can estimate the effect of interventions in the setting of finite resources. From 2005 to 2015, 93 812 eligible individuals were added to the waitlist: 51 322 received deceased donor grafts while 1970 underwent LDLT. Individuals who underwent LDLT had more favourable prognostic factors, including lower mean MELD score at transplant (14.6 vs. 20.5). The 1-year, 5-year and 10-year cumulative incidence of death under the current level of LDLT utilization were 18.0% (95% CI: 17.8, 18.3%), 41.2% (95% CI: 40.8, 41.5%) and 57.4% (95% CI: 56.9, 57.9%) compared to 17.9% (95% CI: 17.7, 18.2%), 40.6% (95% CI: 40.2, 40.9%) and 56.4% (95% CI: 55.8, 56.9%) under a strategy which doubles LDLT utilization. Expansion of LDLT utilization would have a measurable, modest effect on the risk of mortality for the entire cohort of individuals who begin on the transplant waiting list., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience., Methods: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018., Results: We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality., Conclusion: Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe variability in and consequences of opioid prescriptions following pediatric laparoscopic appendectomy., Summary Background Data: Postoperative opioid prescribing patterns may contribute to persistent opioid use in both adults and children., Methods: We included children <18 years enrolled as dependents in the Military Health System Data Repository who underwent uncomplicated laparoscopic appendectomy (2006-2014). For the primary outcome of days of opioids prescribed, we evaluated associations with discharging service, standardized to the distribution of baseline covariates. Secondary outcomes included refill, Emergency Department (ED) visit for constipation, and ED visit for pain., Results: Among 6732 children, 68% were prescribed opioids (range = 1-65 d, median = 4 d, IQR = 3-5 d). Patients discharged by general surgery services were prescribed 1.23 (95% CI = 1.06-1.42) excess days of opioids, compared with those discharged by pediatric surgery services. Risk of ED visit for constipation (n = 61, 1%) was increased with opioid prescription [1-3 d, risk ratio (RR) = 2.46, 95% CI = 1.31-5.78; 4-6 d, RR = 1.89, 95% CI = 0.83-4.67; 7-14 d, RR = 3.75, 95% CI = 1.38-9.44; >14 d, RR = 6.27, 95% CI = 1.23-19.68], compared with no opioid prescription. There was similar or increased risk of ED visit for pain (n = 319, 5%) with opioid prescription [1-3 d, RR = 1.00, 95% confidence interval (CI) = 0.74-1.32; 4-6 d, RR = 1.31, 95% CI = 0.99-1.73; 7-14 d, RR = 1.52, 95% CI = 1.00-2.18], compared with no opioid prescription. Likewise, need for refill (n = 157, 3%) was not associated with initial days of opioid prescribed (reference 1-3 d; 4-6 d, RR = 0.96, 95% CI = 0.68-1.35; 7-14 d, RR = 0.91, 95% CI = 0.49-1.46; and >14 d, RR = 1.22, 95% CI = 0.59-2.07)., Conclusions: There was substantial variation in opioid prescribing patterns. Opioid prescription duration increased risk of ED visits for constipation, but not for pain or refill.

Background: Clinicians and patients may be more interested in per-protocol effect estimates than intention-to-treat effect estimates from randomized trials. However, per-protocol effect estimates may be biased due to insufficient adjustment for prognostic factors that predict adherence. Adjustment for this bias is possible when appropriate methods, such as inverse probability weighting, are used. But, when adherence is measured as a continuous variable, constructing these weights can be challenging., Methods: In the placebo arm of the Lipid Research Clinics Coronary Primary Prevention Trial, we estimated the 7-year cumulative incidence of coronary heart disease under 100% adherence and 0% adherence to placebo. We used dose-response discrete-hazards models with inverse probability weighting to adjust for pre- and post-randomization covariates. We considered several continuous distributions for constructing the inverse probability weights., Results: The risk difference estimate for 100% adherence compared with 0% adherence ranged from -7.7 to -6.1 percentage points without adjustment for baseline and post-baseline covariates, and ranged from -1.8 to 2.2 percentage points with adjustment using inverse probability weights, depending on the dose-response model and inverse probability weight distribution used., Conclusions: Methods which appropriately adjust for time-varying post-randomization variables can explain away much of the bias in the "effect" of adherence to placebo. When considering continuous adherence, investigators should consider several models as estimates may be sensitive to the model chosen.

Competing Interests: Competing interests: None declared.

Partial exchangeability is sufficient for the identification of some causal effects of interest. Here we review the use of common graphical tools and the sufficient component cause model in the context of partial exchangeability. We illustrate the utility of single world intervention graphs (SWIGs) in depicting partial exchangeability and provide an illustrative example of when partial exchangeability might hold in the absence of complete exchangeability.

Background: Intensive surveillance strategies are currently recommended for patients after curative treatment of colon cancer, with the aim of secondary prevention of recurrence. Yet, intensive surveillance has not yielded improvements in overall patient survival compared with minimal follow-up, and more intensive surveillance may be costlier., Objective: The purpose of this study was to estimate the quality-adjusted life-years, economic costs, and cost-effectiveness of various surveillance strategies after curative treatment of colon cancer., Design: A Markov model was calibrated to reflect the natural history of colon cancer recurrence and used to estimate surveillance costs and outcomes., Settings: This was a decision-analytic model., Patients: Individuals entered the model at age 60 years after curative treatment for stage I, II, or III colon cancer. Other initial age groups were assessed in secondary analyses., Main Outcome Measures: We estimated the gains in quality-adjusted life-years achieved by early detection and treatment of recurrence, as well as the economic costs of surveillance under various strategies., Results: Cost-effective strategies for patients with stage I colon cancer improved quality-adjusted life-expectancy by 0.02 to 0.06 quality-adjusted life-years at an incremental cost of $1702 to $13,019. For stage II, they improved quality-adjusted life expectancy by 0.03 to 0.09 quality-adjusted life-years at a cost of $2300 to $14,363. For stage III, they improved quality-adjusted life expectancy by 0.03 to 0.17 quality-adjusted life-years for a cost of $1416 to $17,631. At a commonly cited willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the most cost-effective strategy for patients with a history of stage I or II colon cancer was liver ultrasound and chest x-ray annually. For those with a history of stage III colon cancer, the optimal strategy was liver ultrasound and chest x-ray every 6 months with CEA measurement every 6 months., Limitations: The study was limited by model structure assumptions and uncertainty around the values of the model's parameters., Conclusions: Given currently available data and within the limitations of a model-based decision-analytic approach, the effectiveness of routine intensive surveillance for patients after treatment of colon cancer appears, on average, to be small. Compared with testing using lower cost imaging, currently recommended strategies are associated with cost-effectiveness ratios that indicate low value according to well-accepted willingness-to-pay thresholds in the United States. See Video Abstract at http://links.lww.com/DCR/A921.

Background: The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown., Methods: Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes., Results: One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, -6.7% to -0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, -7.3% to -0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, -7.8% to 11.8%; kidney risk difference, -1.5%; 95% CI, -5.4% to 3.1%)., Conclusions: In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.

Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.

Background: Junctional tourniquets have been incorporated into tactical combat casualty care for junctional vascular trauma. They apply external compression to stop blood flow in the groin and axilla., Objectives: The primary outcome was effectiveness in achieving arterial occlusion. Secondary outcomes included time to application and pain scores., Data Sources: Medline and EMBASE databases were searched., Study Appraisal and Synthesis Methods: A random-effects meta-analysis was conducted to estimate the average effectiveness and time to effective application for each device., Results: Eight studies reported the effectiveness of junctional tourniquets in healthy volunteers. The average effectiveness was 52% (95% confidence interval [CI], 15-87%) for the abdominal application of the abdominal aortic and junctional tourniquet (AAJT), 83% (95% CI, 73-89%; 26%) for the junctional Emergency Treatment Tool, 87% (95% CI, 79-92%; 15%) for the SAM junctional tourniquet (SJT), and 95% (95% CI, 90-98%) for the Combat Ready Clamp. The groin application of the AAJT was studied in two articles with 100% in both studies. The average time to application was 101 seconds for the SAM junctional tourniquet (95% CI, 50-152 seconds) and the Combat Ready Clamp (95% CI, 63-139 seconds), while it was 130 seconds (95% CI, 85-176 seconds) for the Junctional Emergency Treatment Tool. The abdominal application of AAJT had an average time to application of 92 and 171 seconds in two studies., Limitations: All studies were conducted in healthy volunteers., Conclusion and Implications: Junctional tourniquets may meet a medical need in combat, and in the civilian environment, to control hemorrhage from these difficult injuries. All four Food and Drug Administration-approved devices demonstrate the ability to achieve vascular occlusion in healthy volunteers; however, effectiveness in patient transport has not been evaluated, and outcomes of their use in the field need to be captured and reported., Level of Evidence: Systematic review, level III.

Recent literature has raised concerns regarding the risk of adverse psychiatric events among bariatric surgery patients. However, the relationship between weight loss therapy and psychiatric outcomes is confounded by baseline psychosocial characteristics in observational studies. To understand the impact of bariatric surgery on the risk of adverse mental health outcomes, we conducted a systematic review and meta-analysis of randomized controlled trials that compared surgical and non-surgical treatments and assessed mental health quality of life (QoL). We evaluated the PubMed, EMBASE, Web of Science PsycINFO, Clinicaltrials.gov and Cochrane databases through 7 March 2018. Pooled standardized mean differences (SMDs) for mental health QoL scores were estimated using random effects models. Eleven randomized trials with 731 participants were included in the final analyses. Surgery was not associated with an improvement in mental health QoL from baseline as compared to non-surgical intervention (SMD: 0.02, 95% confidence interval [CI] -0.22 to 0.25). Final mental health QoL scores were similar for surgically and non-surgically treated patients (SMD: 0.37, 95% CI -0.07 to 0.81). Subgroup analyses assessing the effect of specific surgical interventions, and varying lengths of follow-up did not identify a beneficial effect of bariatric surgery on mental health QoL outcomes. These results, in conjunction with the fact that individuals who choose bariatric surgery tend to have high-risk baseline characteristics, suggest that intensive mental health follow-up following surgery should be routinely considered., (© 2018 World Obesity Federation.)

Purpose: The relationship between emergency colon cancer resection and long-term oncological outcomes is not well understood. Our objective was to characterize the impact of emergency resection for colon cancer on disease-free and overall patient survival., Methods: Data on patients undergoing resection for colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database. The median follow-up time was 4.4 years. Cox proportional hazards models were used to estimate the hazard ratios for recurrence and death for patients treated with surgery for an emergent presentation. Differences in initiation of, and timeliness of, adjuvant chemotherapy between emergently and electively treated patients were also examined., Results: Of the 1180 patients who underwent resection for stages I, II, or III colon cancer, 158 (13%) had emergent surgery. After adjustment for patient, tumor, and treatment characteristics, the HR for recurrence was 1.64 (95% CI 1.12-2.40) and for death was 1.47 (95% CI 1.10-1.97). After adjustment for tumor characteristics, patients who underwent emergency resection were similarly likely to receive adjuvant chemotherapy (OR 1.1; 95% CI 0.70-1.76). The time from surgery to initiation of adjuvant chemotherapy was also similar between the groups., Conclusions: Emergency surgery for localized or regional colon cancer is associated with a greater risk of recurrence and death. This association does not appear to be due to differences in adjuvant treatment. A focus on screening and colon cancer awareness in order to reduce emergency presentations is warranted.

Purpose: Our objective was to assess 30-day mortality and complication rates associated with percutaneous enteral feeding tube insertion using a single-puncture, dual-suture anchor gastropexy and peel-away sheath technique. We explored differences in complications based on indication and gastrostomy versus gastrojejunostomy tube., Methods: A retrospective review was conducted of adult patients undergoing fluoroscopically guided gastrojejunostomy (GJ) and gastrostomy (G) tube insertions between July 2011 and 2014 by five interventional radiologists at a single tertiary care centre. A single-puncture dual-anchor gastropexy technique with a peel-away sheath was used for all patients. Complications within 30 day post-procedure were classified based on the Society of Interventional Radiology Standards of Practice for Gastrointestinal Access. Procedure-related mortality and complication rates, as well as indication-specific complication rates, were compared between GJ and G groups., Results: 559 consecutive patients underwent G (86) or GJ (473) tube insertion. Primary technical success was 100%. Nine major (1.6%) and 60 minor (10.7%) complications occurred for an overall complication rate of 12.3%. The 30-day complication rate was significantly higher for GJ compared to G tube insertion (13.5% v. 5.8%, p = .049). There was a trend toward a higher 30-day minor complication rate for the GJ group (11.8% v. 4.7%, p = .057), but no significant difference between groups with respect to major complications (1.7% v. 1.2%, p = 1.0). Four procedure-related deaths occurred resulting in an overall procedure-related mortality of 0.7%. No significant difference in the procedure-related mortality was found between GJ and G groups (0.6% v. 1.2%, p = .49)., Conclusion: The 30-day major complication and procedure-related mortality rates from G and GJ tube insertion are low when using a single-puncture, dual-anchor gastropexy technique. GJ tube insertion is associated with a higher overall complication rate, likely due to more minor complications, but may avoid long-term adverse events., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative, 2-staged hepatectomy which has elicited controversy within the international hepatobiliary community. Uptake of ALPPS has been limited due to concerns related to evidence of high morbidity and mortality, and scant oncologic and outcome data on quality of life (Qol). Demonstrating reasonable long-term benefits with a short-term risk is necessary to support more widespread endorsement of ALPPS. Our aim was to describe the intermediate-term survival and patient-reported quality of life outcomes after an ALPPS., Methods: Prospectively collected data from 2 high-volume ALPPS centers, who were pioneers with the technique, were combined and analyzed for disease-free and overall survival from date of the ALLPS. Only patients treated for colorectal liver metastases with >6 month postoperative follow-up were included. All patients had bilateral colorectal liver metastases with an initially unresectable tumor load, and received preoperative chemotherapy. Information concerning the demographics of the patients, characteristics of the tumor, and treatment were analyzed. The well-validated European Organization for Research and Treatment for Cancer Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess patient quality of life., Results: A total of 58 patients underwent ALPPS for colorectal liver metastases, and 47 patients met our inclusion criteria. There were no perioperative mortalities, and the rate of severe complications was 21%. At 3 years post-ALPPS, the overall survival was 50%, while the disease-free survival was 13%. The commonest site of first recurrence was the liver alone (38%). Patient-reported quality of life after ALPPS was similar to reference values for general population., Conclusion: In select patients operated at experienced centers, ALPPS results in low perioperative risk, satisfactory overall survival, and excellent quality of life. Hepatic recurrence and not systemic recurrence is the most common site of relapse after ALPPS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Studies examining treatment delay and survival after surgical treatment of colon cancer have varied in quality and outcome, with little evidence available regarding the safety of longer surgical treatment wait times., Objective: Our study examined the effect of surgical treatment wait times on survival for patients with stage I to III colon cancer., Design: A subset cohort analysis was performed using data from a prospectively maintained database., Settings: The study was conducted at a tertiary referral center., Patients: Data on all of the patients undergoing elective surgery for stage I to III colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database., Main Outcome Measures: We examined the impact of prolonged wait time to surgery on disease-free and overall survival. Patients were divided into 2 groups based on a treatment wait time of ≤30 or >30 days and were compared using a Cox proportional hazards model. A subgroup analysis was performed using alternative treatment delay cutoffs of 60 and 90 days., Results: There were 908 patients with stage I to III colon cancer treated over the study period, with a median treatment wait time of 38 days (interquartile range, 21-61 days); 368 patients were treated within 30 days, and 540 were treated beyond 30 days from diagnosis. In adjusted multivariate analysis, a treatment delay of >30 days was not associated with decreased disease-free survival (HR = 0.89 (95% CI, 0.61-1.3); p = 0.52) or overall survival (HR = 0.82 (95% CI, 0.63-1.1); p = 0.16). Likewise, subgroup analysis using alternative treatment delay cutoffs of 60 and 90 days did not demonstrate an adverse effect on survival., Limitations: This study was limited by retrospective analysis., Conclusions: Despite longer median treatment wait times from diagnosis to surgery, with the majority of patients exceeding 30 days and many experiencing delays of 2 to 3 months, no adverse impact on survival was observed. Patients who require additional consultations or investigations preoperatively may safely have their surgery moderately delayed to minimize their perioperative risk without any evidence that this will compromise treatment outcomes. See Video Abstract at http://links.lww.com/DCR/A397.

Background: Early reports of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) outcomes have been suboptimal. The literature has confirmed that learning curves influence surgical outcomes. We have 54 months of continuous experience performing ALPPS with strict selection criteria. This study aimed to evaluate the impact of the learning curve on ALPPS outcomes., Methods: We retrospectively compared patients who underwent ALPPS between April 2012 and March 2016. Patients were grouped into 2 24-month (early and late) periods. All candidates had a high tumour load requiring staged hepatectomy after chemotherapy response, a predicted future liver remnant (FLR) less than 30% and good performance status., Results: Thirty-three patients underwent ALPPS during the study period: 16 in the early group (median age 65 yr, mean body mass index [BMI] 27) and 17 in the late group (median age 60 yr, mean BMI 25). Bilobar disease was comparable in both groups (94% v. 88%, p > 0.99). Duration of surgery was not statistically different. Intraoperative blood loss and need for transfusion were significantly lower in the late group (200 ± 109 mL v. 100 ± 43 mL, p < 0.05). The late group had a higher proportion of monosegment ALPPS (4:1). There were no deaths within 90 days in either cohort. Rates of postoperative complications were not statistically significant between groups. The R0 resection rate was similar. The entire 1-year disease-free and overall survival were 52% and 84%, respectively., Conclusion: Excellent results can be obtained in innovative complex surgery with careful patient selection and good technical skills. Additionally, the learning curve brought confidence to perform more complex procedures while maintaining good outcomes.

Background: Duration of functional warm ischemia (f-WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT)., Methods: A retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F-WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non-function (PNF), and early graft failure., Results: 35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f-WIT variations analyzed, only f-WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications., Conclusion: This study demonstrates that, of the f-WITs, f-WIT with SpO2 ≤ 60% is most predictive of post-DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: While no evidence exists to support mandatory multidisciplinary case conference (MCC) review for patients with synchronous colorectal cancer and liver metastases, this unique population may benefit greatly from multidisciplinary discussion., Methods: We retrospectively identified patients who underwent liver resection with curative intent for colorectal liver metastases (CRLM) at a tertiary center between January 2008 and June 2015. The characteristics of patients discussed at a weekly regional MCC were examined, and the effect of MCC review on treatment approach was assessed., Results: Sixty-six patients underwent elective surgery for synchronous colorectal cancer and liver metastases during the study period. Twenty-nine patients (44%) were presented at a MCC. Presentation was associated with greater likelihood of undergoing simultaneous or liver-first resection (P≤0.0001), with no difference in the extent of liver resection or location of primary tumor between the groups. A greater proportion of patients received chemotherapy and/or radiation following MCC discussion, without statistical significance., Conclusions: The treatment approach for patients with synchronous colorectal cancer and liver metastases may be significantly altered based on MCC review. Multidisciplinary discussion is advocated in order to facilitate equal access to individualized care., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data., Methods: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2., Results: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively., Conclusions: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2.

Background: Hemorrhoidectomy is associated with significant postoperative pain. Oral metronidazole has been recommended as an adjunct to improve posthemorrhoidectomy analgesia., Objective: This study aimed to evaluate the impact of oral metronidazole on patient-reported pain following hemorrhoidectomy., Data Sources: We conducted a systematic search in the MEDLINE, EMBASE, ISI Web of Science, and Cochrane Central Register of Controlled Trials databases., Study Selection: Randomized controlled trials examining adults who underwent surgical hemorrhoidectomy were included. Participants in an active intervention group received oral metronidazole postoperatively, and those in a control group received placebo or usual care. Postoperative pain was assessed for at least 3 days postoperatively., Intervention: A random-effects model was used., Main Outcomes Measures: The primary outcome was pain during the first 2 postoperative weeks, measured on a visual analogue scale. The secondary outcome was time to return to normal activities., Results: Patients who received oral metronidazole had significantly lower reported pain scores on postoperative day 1 (standardized mean difference, -0.87 ± 0.44; 95% CI, -1.73 to -0.015; p = 0.046; n = 4) and day 4 (standardized mean difference, -1.43 ± 0.71; 95% CI, -2.83 to -0.037; p = 0.044; n = 3). Metronidazole use was associated with a significantly shorter time to return to normal activities (standardized mean difference, -0.76 ± 0.34; 95% CI, -1.43 to -0.088, p = 0.027). The improvements disappeared in a sensitivity analysis excluding the largest trial with a high risk of bias, and no significance was observed during the remaining postoperative days., Limitations: The meta-analysis was limited by lack of double blinding, absence of a placebo, and unclear or high risk of bias in a proportion of the included trials., Conclusions: Although a favorable adverse effect profile supports consideration of oral metronidazole to reduce posthemorrhoidectomy pain, pooled analysis reveals inconsistent results with no pain reduction on most postoperative days. The current recommendation for routine prescription of oral metronidazole should be reevaluated in the absence of additional well-designed trials.

Background: Adrenocortical carcinoma is a rare cancer, with an incidence in the literature of 0.5 to 2 cases per million population per year. Adult adrenocortical carcinoma has a poor prognosis, underscoring the importance of identifying diagnostic and prognostic markers., Methods: We searched our laboratory database for all cases in the past 15 years with a diagnosis of adrenocortical carcinoma. The original slides were then reviewed for their histopathological features. A representative paraffin block was subjected to further immunohistochemical staining for Ki-67, inhibin, steroidogenic factor-1 (SF-1), p53, and Β-catenin. These slides were scored by the study pathologist who was blinded to all clinicopathological data. In addition, a comprehensive review of the relevant English literature in the past 15 years was conducted., Results: Eight cases were identified, including two adrenal sarcomatoid carcinomas. Seven of the eight cases had a disrupted reticulin network. Six of the eight tumors had >10% Ki-67 expression. Five of the eight tumors had >10% p53 expression. Positive inhibin immunohistochemical staining was seen in three of the eight tumors, and positive SF-1 staining was seen in five of the seven stained tumors. Abnormal Β-catenin intracellular accumulation was noted in four of the eight tumors. The two tumors in our series with sarcomatoid histology did not stain positively for SF-1 or inhibin., Conclusions: Eight cases of adrenocortical carcinoma, including two with sarcomatoid features are presented. The two sarcomatoid adrenocortical carcinomas in our series did not stain for SF-1 which suggests a possible de novo pathway of tumorigenesis for this rare variant. The reticulin staining method was a useful tool for rapid differentiation of adrenocortical adenomas and carcinomas. Diffuse p53 staining showed a trend for positive correlation with increased Ki-67 expression. Inhibin staining was inconsistently expressed in our cases of adrenocortical carcinoma. In conclusion, as adrenocortical carcinoma is a rare disease, we recommend future multicenter studies with appropriate sample sizes to further evaluate the efficacy of these diagnostic and prognostic markers.

Introduction: In January 2012 an acute care surgery (ACS) model was introduced at St. Paul's Hospital, Saskatoon, Saskatchewan. The goal of implementing an ACS service was to improve the delivery of care for emergent, non-trauma surgical patients. We examined whether the ACS model improved wait time to surgery, decreased the proportion of surgeries performed after hours, and shortened post-surgical length of stay. We also assessed whether the surgeons working in an ACS system had higher on-call satisfaction than surgeons working in a non- ACS system., Methods: A retrospective pre-post analysis was performed using data from the Discharge Abstract Database and the Organizing Medical Networked Information database. Surgeon satisfaction was evaluated using a questionnaire that was mailed to all general surgeons in Saskatoon., Results: An ACS service significantly reduced wait time to surgery for patients with all acute general surgery diagnoses from 221 minutes to 192 minutes (ρ = 0.015; CI = 5.8-52.2). Post-surgery length of stay for patients operated on for acute appendicitis, or acute cholecystitis was not reduced. On average, patients with bowel obstruction had increased length of stay following ACS service implementation. Most surgeries in our study were performed between 16:00 hours and 08:00 hours but the introduction of an ACS significantly reduced the number of afterhours surgeries (60.0% vs. 72.6%) (ρ < 0.0001). Our survey had a response rate of 75%. Overall, surgeons on an ACS service had greater satisfaction with the organization of their call schedule than surgeons not on an ACS service., Conclusion: Introduction of an ACS service in Saskatoon has decreased wait time to surgery and reduced the proportion of afterhours emergency surgeries, with no reduction in the length of post-surgery hospital stay. Satisfaction may be higher for surgeons in an ACS service.