Bias estimation in study design: a meta-epidemiological analysis of transcatheter versus surgical aortic valve replacement.

BACKGROUND: Paucity of RCTs of non-drug technologies lead to widespread dependence on non-randomized studies. Relationship between nonrandomized study design attributes and biased estimates of treatment effects are poorly understood. Our purpose was to estimate the bias associated with specific nonrandomized study attributes among studies comparing transcatheter aortic valve implantation with surgical aortic valve replacement for the treatment of severe aortic stenosis. RESULTS: We included 6 RCTs and 87 nonrandomized studies. Surgical risk scores were similar for comparison groups in RCTs, but were higher for patients having transcatheter aortic valve implantation in nonrandomized studies. Nonrandomized studies underestimated the benefit of transcatheter aortic valve implantation compared with RCTs. For example, nonrandomized studies without adjustment estimated a higher risk of postoperative mortality for transcatheter aortic valve implantation compared with surgical aortic valve replacement (OR 1.43 [95% CI 1.26 to 1.62]) than high quality RCTs (OR 0.78 [95% CI 0.54 to 1.11). Nonrandomized studies using propensity score matching (OR 1.13 [95% CI 0.85 to 1.52]) and regression modelling (OR 0.68 [95% CI 0.57 to 0.81]) to adjust results estimated treatment effects closer to high quality RCTs. Nonrandomized studies describing losses to follow-up estimated treatment effects that were significantly closer to high quality RCT than nonrandomized studies that did not. CONCLUSION: Studies with different attributes produce different estimates of treatment effects. Study design attributes related to the completeness of follow-up may explain biased treatment estimates in nonrandomized studies, as in the case of aortic valve replacement where high-risk patients were preferentially selected for the newer (transcatheter) procedure.

Superior Mesenteric Vein-First Approach to Robotic Complete Mesocolic Excision for Right Colectomy: Technique and Preliminary Outcomes.

INTRODUCTION: There is growing evidence supporting complete mesocolic excision as the optimal surgical approach for right-sided colon cancer to improve oncologic outcomes in comparison with conventional surgical resection. Although the feasibility of a minimally invasive approach to complete mesocolic excision has been reported, obesity has been associated with increased difficulty for finding the correct plane for dissection and delineating the vascular anatomy. We describe a novel approach with early identification of and dissection along the superior mesenteric vein during robotic complete mesocolic excision surgery, for all patients, regardless of BMI. TECHNIQUE: The dissection is initiated with identification of the superior mesenteric vein as the starting point. Then, the vascular dissection is performed along the anterior superior mesenteric vein plane while observing complete mesocolic excision principles. The anterior superior mesenteric vein plane is an optimal and safe dissection plane because there are no anterior tributaries. The ileocolic vein and artery are ligated separately at their junction with the superior mesenteric vein and superior mesenteric artery. The dissection is then continued cephalad along the superior mesenteric vein, identifying additional colic arteries, including the middle colic arterial trunk as well as the venous tributaries to the superior mesenteric vein such as the gastrocolic trunk. The superior right colic vein is then ligated at the gastrocolic confluence and the middle colic vessels are ligated. After the vascular dissection is completed, the colon is then mobilized. RESULTS: A total of 66 patients received the "superior mesenteric vein-first" approach for robotic colectomy between 2013 and 2018, including 40.9% patients with BMI >30 kg/m. Median lymph node yield was 32 (interquartile range, 25-40). The median distance to the high vascular tie was 12 cm (interquartile range, 7-19). Median estimated blood loss was 33 mL (interquartile range, 25-50). Overall rate of grade ≥3 complications was 3.0%. CONCLUSIONS: Using the superior mesenteric vein-first approach, robotic complete mesocolic excision for right colectomy can be performed on patients with high or low BMI with excellent short-term oncologic outcomes and acceptable morbidity. See Video Abstract at http://links.lww.com/DCR/A960.

Practice patterns for the management of hepatic metastases from colorectal cancer: a mixed methods analysis.

PURPOSE: The optimal management of colorectal cancer liver metastases (CRC-LM) has changed during the past two decades. However, clinical practice lags behind best evidence recommendations. We sought to characterize the gap between current practice and best evidence for the management of these patients and to identify barriers that hamper effective utilization of metastasectomy. METHODS: A mixed-methods approach was used. A survey was mailed to all general surgeons (GS) and medical oncologists (MO) in Ontario, Canada. Domains examined included: physician/practice characteristics, indications for hepatectomy, use of multi-modality therapy and referral patterns. Physician focus groups were conducted that explored issues relating to access to care. RESULTS: The survey was mailed to 942 physicians with a response rate of 68 % (n = 348; GS n = 295, 69 %; MO n = 53, 63 %). Current practice patterns demonstrated that 97 % of physicians refer patients with low tumor burden (e.g., solitary CRC-LM), but referral rates for hepatectomy decreased as the tumor burden increased. Physicians still consider extrahepatic disease as a strong contraindication to metastasectomy. Barriers to care included: economic, time, and resource constraints; lack of physician engagement, local medical expertise, and high-quality guidelines. Multidisciplinary cancer conferences were identified as an enabler of clinical care and a potential platform for the acquisition of new medical knowledge. CONCLUSIONS: Current management of CRC-LM does not reflect best evidence. Patients who may benefit from surgery are not being referred for metastasectomy. We have identified an evidence-practice gap at the level of physician, which should be targeted with novel quality improvement strategies.

Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis.

Experimental studies suggest that the regenerating liver provides a "fertile field" for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease-free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta-analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non-randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02-2.49; I(2) = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73-1.27; I(2) = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.

Quality of narrative operative reports in pancreatic surgery.

BACKGROUND: Quality in health care can be evaluated using quality indicators (QIs). Elements contained in the surgical operative report are potential sources for QI data, but little is known about the completeness of the narrative operative report (NR). We evaluated the completeness of the NR for patients undergoing a pancreaticoduodenectomy. METHODS: We reviewed NRs for patients undergoing a pancreaticoduodenectomy over a 1-year period. We extracted 79 variables related to patient and narrator characteristics, process of care measures, surgical technique and oncology-related outcomes by document analysis. Data were coded and evaluated for completeness. RESULTS: We analyzed 74 NRs. The median number of variables reported was 43.5 (range 13-54). Variables related to surgical technique were most complete. Process of care and oncology-related variables were often omitted. Completeness of the NR was associated with longer operative duration. CONCLUSION: The NRs were often incomplete and of poor quality. Important elements, including process of care and oncology-related data, were frequently missing. Thus, the NR is an inadequate data source for QI. Development and use of alternative reporting methods, including standardized synoptic operative reports, should be encouraged to improve documentation of care and serve as a measure of quality of surgical care.

CONTEXTE: Il est possible d'évaluer la qualité des soins de santé au moyen d'indicateurs de qualité (IQ). Les éléments contenus dans les notes opératoires (NO) sont une source potentielle de renseignements pouvant servir d'IQ, mais on en sait peu sur leur exhaustivité. Nous avons voulu évaluer l'exhaustivité des NO dans les dossiers de patients soumis à une pancréatoduodénectomie. MÉTHODES: Nous avons passé en revue les NO dans les dossiers de patients soumisà une pancréatoduodénectomie sur une période d'un an. Par analyse des documents, nous avons extrait 79 variables liées aux caractéristiques des patients et aux rédacteurs des NO, aux mesures des protocoles opératoires, à la technique chirurgicale et aux résultats oncologiques. Nous avons encodé et évalué ces données en fonction de leur exhaustivité. RÉSULTATS: Nous avons analysé les NO pour 74 interventions. Le nombre médian de variables relevées était de 43,5 (entre 13 et 54). Les variables liées au protocole de soins et les variables oncologiques étaient souvent omises. L'exhaustivité des NO était proportionnelle à la durée de l'intervention. CONCLUSION: Les NO sont souvent incomplètes et leur qualité laisse à désirer. Des éléments importants, dont le protocole opératoire et les données oncologiques, étaient souvent manquants. Ainsi, les NO constituent une source inadéquate de données en ce qui concerne les IQ. Il faudra encourager la mise au point et l'utilisation d'autres types de rapports, dont des synopsis opératoires standardisés, pour mieux documenter les soins chirurgicaux prodigués et pour en évaluer la qualité.

Breast Cancer Recurrence by Subtype in a Diverse, Contemporary Cohort of Young Women.

BACKGROUND: Young breast cancer (YBC) patients are a unique subpopulation that are often underrepresented in randomized clinical trials. Furthermore, large national cancer databases lack detailed information on recurrence, a meaningful oncologic outcome for young patients. STUDY DESIGN: A retrospective review of YBC patients (age 40 years or younger) with stage I to III breast cancer diagnosed from 2008 to 2018 was performed. Information on clinicopathologic characteristics, demographics, and outcomes was obtained from the electronic health record and chart review. Chi-square and Fisher's exact tests were used for comparisons of categorical variables and parametric and nonparametric tests for continuous variables. RESULTS: The cohort included 1,431 women with a median follow-up of 4.8 years (range 0.3 to 12.9 years). The median age was 37 years (interquartile range 34 to 39). The study population included 598 (41.8%) White, 112 (7.8%) Black, 420 (29.4%) Asian/Pacific Islander, 281 (19.6%) Hispanic, and 20 (1.4%) "other" race/ethnicity patients. Tumor subtype was as follows: [1] hormone receptor (HR) + /human epidermal growth factor 2 (HER2 - ), grade (G) 1 to 2 = 541 (37.8%); [2] HR + /HER2 - , G3 = 268 (18.7%); [3] HR + /HER2 + = 262 (18.3%); [4] HR - /HER2 + = 101 (7.1%); [5] HR - /HER2 - = 259 (18.1%). The majority (64.2%) presented with stage II/III disease. There were 230 (16.1%) recurrences during follow-up; 74.8% were distant. Locoregional-only recurrence was seen in 17 of 463 (3.7%) patients who underwent breast conservation vs 41 of 968 (4.2%) patients undergoing mastectomy (p < 0.001). Recurrence varied by tumor subtype: [1] HR + /HER2 - , G1 to 2 (14.0%); [2] HR + /HER2 - , G3 (20.9%); [3] HR + /HER2 + (11.1%); [4] HR - /HER2 + (22.8%); [5] HR - /HER2 - (17.8%) (p = 0.005). CONCLUSIONS: In this large, diverse YBC cohort, recurrences were most frequent among HR + /HER2 - , G3, or HR - /HER2 + invasive tumors; most were distant. There were numerically similar locoregional-only recurrences after breast conservation vs mastectomy. Additional research is needed to identify predictors of recurrence.

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: comparable survival and recurrence.

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow-up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1-, 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC.

Assessing the management of hepatic colorectal cancer metastases: is treatment consistent in Ontario?

OBJECTIVES: Advances in surgical techniques and chemotherapeutic options have expanded indications for surgery in patients with metastatic colorectal cancer. This study aimed to examine how hepatopancreatobiliary (HPB) surgeons approach the management of patients with hepatic colorectal cancer metastases (HCCM). METHODS: A web-based survey utilizing 10 clinical scenarios was distributed by e-mail to 37 HPB surgeons in Ontario, Canada. The study region has a population of approximately 13 million people and a universal, single-payer health care system. Descriptive analyses were used to tabulate results. RESULTS: Twenty-two (59%) surgeons responded to the survey. The majority (19/22, 86%) of respondents favoured neoadjuvant chemotherapy for patients with multiple synchronous and unilobar metastases; only nine of 22 (41%) respondents favoured neoadjuvant chemotherapy for patients with a single synchronous metastasis. In the setting of residual resectable disease following downstaging chemotherapy, 77% (17/22) of surgeons advocated hepatic resection with either radiofrequency ablation (RFA) or wedge resection of the 'ghost' lesions. Over 80% of surgeons would perform a liver and pulmonary resection in a patient with hepatic and multiple unilobar lung metastases. None would offer liver resection to patients with multiple retroperitoneal node involvement, although 55% (12/22) would do so if a single retroperitoneal node was involved. Preoperative portal vein embolization was favoured over RFA in patients with a small metastasis and inadequate functional hepatic volume. CONCLUSIONS: Notable heterogeneity was observed among Ontario's HPB surgeons in approaches to HCCM.

Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion.

BACKGROUND: Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors. OBJECTIVE: We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy. METHODS: Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008. RESULTS: Imaging understaged 30% of the M group and over staged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031). CONCLUSIONS: Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.

Tumor Sidedness, Recurrence, and Survival After Curative Resection of Localized Colon Cancer.

BACKGROUND: Right-sided primary tumor location is associated with worse prognosis in metastatic colon cancer, but the effect of sidedness on recurrence and prognosis for non-metastatic disease is less understood. The purpose of this study was to examine the relationship between sidedness, recurrence, and survival among patients with localized colon cancer. PATIENTS AND METHODS: Consecutive patients who underwent curative resection of colon cancer (2006-2013) were identified from a prospective database and retrospectively analyzed. Risk for recurrence, overall survival, and survival after recurrence (SAR) were compared between left- and right-sided tumors using the log-rank test, and multivariable Cox proportional hazards regression. RESULTS: We evaluated 673 patients (347 right-sided). There was no difference in overall recurrence rates (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.54-1.55; P = .75) or overall survival (HR, 1.22; 95% CI, 0.75-1.97; P = .42) between right- and left-sided primary tumors. However, right-sided tumors were more likely to develop multi-focal and poor prognostic site recurrence (P = .04). Among the 71 patients who developed recurrence, those with right-sided tumors had significantly lower SAR (HR, 3.88; 95% CI, 1.42-10.62; P = .008). CONCLUSIONS: Among patients with colon cancer who underwent curative resection, tumor sidedness was not associated with recurrence risk. However, among patients who developed recurrence, right-sidedness was associated with unique recurrence patterns and inferior SAR. For patients presenting with localized disease, treatment stratification should not be based on tumor sidedness alone.

Contralateral prophylactic mastectomy rate stable at major Canadian breast cancer center.

AIM: To examine trends of contralateral prophylactic mastectomy (CPM) rates at a Canadian academic breast cancer center. METHODS: A single-institution retrospective cohort study was completed. Women of any age who underwent at least a unilateral mastectomy (UM) for primary unilateral breast carcinoma between January 1, 2004 and December 31, 2010 were included. Patients who underwent CPM on the same day as UM were isolated to create two distinct cohorts. Patient and procedure characteristics were compared across groups using R software (version 3.1.0). The percentage of CPMs per year was determined. The Cochrane-Armitage test was used to assess the trend of CPMs over time. A P value of < 0.05 was considered significant. RESULTS: A total of 811 women met the inclusions/exclusion criteria; 759 (93.6%) underwent UM alone and 52 (6.4%) underwent UM with immediate CPM. The absolute number of procedures (UM and UM + CPM) increased over time, from 83 in 2004 to 147 in 2010 reflecting an increase in mastectomy volume. Annual CPM rates did not increase over time (P = 0.7) and varied between 2.6% to 10.7%. Family history of breast cancer [OR 3.6 (1.8-7.3)] and immediate reconstruction [10.0 (5.2-19.3)] were both significantly associated with CPM. Women who underwent CPM were younger (median age CPM 49 years vs UM 52 years, P < 0.0001) but age less than 50 years was not statistically associated with increased rates of CPM. CONCLUSION: CPM rates from 2004 to 2010 at a high-volume Canadian breast cancer center did not increase over time, in contrast to trends observed in the United States.