Distinguishing Clinical From Statistical Significances in Contemporary Comparative Effectiveness Research.

OBJECTIVE: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). BACKGROUND: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase health care costs and treatment toxicity. METHODS: CER studies from 2022 issues of the Annals of Surgery , Journal of the American Medical Association , Journal of Clinical Oncology , Journal of Surgical Research , and Journal of the American College of Surgeons were systematically reviewed by 2 different investigators. The primary outcome of interest was whether the authors specified what they considered to be a clinically significant difference in the "Methods." RESULTS: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size ( r = -0.30, P = 0.038). CONCLUSIONS: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical decision-making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards.

Increasing Trainee Engagement in Surgery Societies: The Society of Asian Academic Surgeons Experience.

INTRODUCTION: Surgical societies provide a plethora of resources for trainees; however, these opportunities are often underused due to suboptimal guidance, sponsorship, or mentorship. Here, we present the Society of Asian Academic Surgeons (SAAS) experience in enhancing the trainee experience and engagement in a surgical society focused on professional development. MATERIALS AND METHODS: We conducted an interactive idea-generating session during the 2022 SAAS Conference with all Associate Members (trainees) present in Honolulu, HI. Recurrent themes, concepts, and ideas/suggestions were carefully considered when planning the next SAAS Conference in Baltimore, MD. We employed a more targeted approach to trainee engagement at the 2023 SAAS Conference, with breakout sessions geared toward various levels of trainees, in addition to increased social events and networking opportunities. We obtained feedback from trainees in attendance through an electronic survey and informal conversations with faculty and Associate Members. RESULTS: Opportunities for surgical subspecialty networking was the most well-received portion of our formal Career Development program. The majority of trainees in attendance were medical students or junior residents who valued the exposure to junior faculty and those in leadership positions at academic institutions. The addition of a group text for easy communication among trainees and informal social activities for Associate Member networking among themselves were crucial in improving the overall conference experience. CONCLUSIONS: Opportunities to maximize trainee engagement in surgical societies are heightened during in-person conferences. Targeted session topics, guided networking opportunities, and creating channels for easier communication along with more social events have enhanced the overall experience for aspiring and current surgical trainees.

Critical Appraisal of Content Quality of YouTube Videos on the Whipple Pancreaticoduodenectomy.

INTRODUCTION: The coronavirus pandemic has demonstrated profound issues with using the Internet to research health information. For patients recommended a complex operation, such as the Whipple pancreaticoduodenectomy, the quality of health information online has not been appraised. The objective of this study was to define the readability and content quality of YouTube search results for the Whipple pancreaticoduodenectomy. METHODS: The first 100 search results for "whipple procedure" less than 10 min long in English with audio and or text were transcribed. The Flesch-Kincaid Grade defined the reading grade level. High content quality videos were accredited by YouTube in accordance with principles specified by the National Academy of Medicine or mentioned the standard components for a surgical consent. The Anderson-Lau score is a composite of these consent criteria out of a maximum of 8/8. The simplicity of videos for patient education was defined by the DISCERN tool. RESULTS: The reading level of 23% of the top 100 search results met the American average (8th grade). Accreditation was present for 45% and associated with an earlier median search ranking (36 versus 68, P = 0.002) and more 5th-8th grade level material (70% versus 38%, P = 0.014). The median Anderson-Lau score was 3/8 (range = 0/8-7/8) with only 5% achieving 7/8. Only 4% were high quality per DISCERN. CONCLUSIONS: Although accredited videos were more readable, most videos, especially those targeting patients, were beyond the comprehension of the average American. Simpler and higher quality educational materials are needed to inform patients on Whipple pancreaticoduodenectomy beyond their date of clinical diagnosis or surgical consenting.

Peribiliary cysts masquerading as choledocholithiasis.

Video 1The major papilla was cannulated with a sphincterotome over a straight wire. The polypoid saccular structures were identified by cholangioscopy.

Robotic Function-Preserving Resection of Gastric Gastrointestinal Stromal Tumor.

INTRODUCTION: Gastric gastrointestinal stromal tumors (GISTs) located at the gastroesophageal junction (GEJ), lesser curvature, posterior gastric wall, or antrum present challenges for gastric function preservation. The aim of this study was to evaluate safety and effectiveness of robot-assisted resection of gastric GIST in challenging anatomic locations. METHODS: This was a single-center case series of robotic gastric GIST resections in challenging anatomic locations performed from 2019 to 2021. GEJ GISTs are defined as tumors within 5 cm of the GEJ. Location of the tumor and distance from the GEJ were determined from the endoscopy report and/or cross-sectional imaging and operative findings. RESULTS: There were 25 consecutive patients who underwent a robot-assisted partial gastrectomy for a gastric GIST in challenging anatomic locations. Tumors were located at the GEJ (n = 12), lesser curvature (n = 7), posterior gastric wall (n = 4), fundus (n = 3), greater curvature (n = 3), and antrum (n = 2). Median distance of tumor from GEJ was 2.5 cm. Both GEJ and pylorus were successfully preserved in all patients regardless of tumor location. Median operative time was 190 min with a median estimated blood loss of 20 mL and no conversion to open approach. Median hospital stay was 3 d with solid diet intake starting 2 d after surgery. Two (8 %) patients had Grade III or higher postoperative complications. Median tumor size upon resection was 3.9 cm. Negative margins were obtained in 96.3%. There was no evidence of recurrent disease with a median follow-up of 11.3 mo. CONCLUSIONS: We demonstrate the safety and feasibility of using the robotic approach to facilitate function preservation gastrectomy in challenging anatomic locations without compromising oncologic resection.

Computerized Diagnosis of Liver Tumors From CT Scans Using a Deep Neural Network Approach.

The liver is a frequent site of benign and malignant, primary and metastatic tumors. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers, and colorectal liver metastasis (CRLM) is the most common secondary liver cancer. Although the imaging characteristic of these tumors is central to optimal clinical management, it relies on imaging features that are often non-specific, overlap, and are subject to inter-observer variability. Thus, in this study, we aimed to categorize liver tumors automatically from CT scans using a deep learning approach that objectively extracts discriminating features not visible to the naked eye. Specifically, we used a modified Inception v3 network-based classification model to classify HCC, ICC, CRLM, and benign tumors from pretreatment portal venous phase computed tomography (CT) scans. Using a multi-institutional dataset of 814 patients, this method achieved an overall accuracy rate of 96%, with sensitivity rates of 96%, 94%, 99%, and 86% for HCC, ICC, CRLM, and benign tumors, respectively, using an independent dataset. These results demonstrate the feasibility of the proposed computer-assisted system as a novel non-invasive diagnostic tool to classify the most common liver tumors objectively.

First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass.

Synovial sarcoma usually presents in the lower extremities and metastasizes to the lungs; however, unusual patterns of recurrence can occur. For patients with recurrent synovial sarcoma to a proximal peripancreatic lymph node, a pancreaticoduodenectomy or Whipple procedure is the best option for a cure. Lymph node metastasis from synovial sarcoma is exceptionally rare, and data guiding the use of the Whipple procedure for curative resection of metastatic synovial sarcoma are even more sparse. In this report, we describe the management of a patient with metastatic synovial sarcoma to a proximal peripancreatic lymph node with a pancreaticoduodenectomy.

Genomic Predictors of Recurrence Patterns After Complete Resection of Colorectal Liver Metastases and Adjuvant Hepatic Artery Infusion Chemotherapy.

BACKGROUND: Despite curative hepatectomy, most colorectal liver metastasis (CRLM) patients relapse locally within 2 years. Genomic predictors for hepatic recurrence are poorly understood. This study was designed to identify genomic signatures for recurrence in resected CRLM patients treated with adjuvant hepatic artery infusion (HAI) and/or systemic (SYS) chemotherapy. METHODS: Patients undergoing curative hepatectomy and adjuvant HAI+SYS or SYS between January 2000 and October 2017 with next-generation sequencing data were catalogued. Gene and signaling-level alterations were checked for association with time to any (AR), liver (LR), and extrahepatic recurrence (ER) by using Kaplan-Meier analysis. RESULTS: Of 172 receiving HAI+SYS, 100 patients recurred, with 69 LR and 83 ER. Five- and ten-year LR-free rates were 57% (95% confidence interval [CI] 48-65%) and 51% (95% CI 41-60%), respectively. Five- and 10-year ER-free, rates were 51% (95% CI 43-58%) and 45% (95% CI 36-54%), respectively. More ER was observed with tumors harboring altered KRAS (38% [95% CI 25-50%] vs. 63% [95% CI 53-71%], p-adj = 0.003) and RAS/RAF (36% [95% CI 25-48%] vs. 66% [95% CI 56-74%], p-adj < 0.001) than wild-type. Co-altered RAS/RAF-TP53 was associated with worse AR (26% [95% CI 14-40%] vs. 48% [95% CI 39-57%], p-unadj < 0.001), ER (30% [95% CI 17-45%] vs. 62% [95% CI 53-70%], p-unadj < 0.001), and LR rate (40% [95% CI 24-57%] vs. 70% [95% CI 60-77%], p-unadj = 0.002). On multivariable analysis, controlling for clinical risk score, ablation, margin status, and primary T-stage, co-altered RAS/RAF-TP53 was associated with increased risk for AR (HR = 2.14, 95% CI 1.38-3.31, p-unadj < 0.001), LR (HR = 1.79, 95% CI 1.06-3.02, p-unadj = 0.029), and ER (HR = 2.81, 95% CI 1.78-4.44, p-unadj < 0.001). CONCLUSIONS: Altered KRAS, RAS/RAF, and RAS/RAF-TP53 associated with earlier local and distant recurrence in resected CRLM patients receiving adjuvant HAI+SYS. Co-altered RAS/RAF-TP53 was a novel predictor of LR warranting investigation of whether genomic cooperativity is associated with this relapsing phenotype. Systemic therapies tailored to high-risk tumor biology are needed to reduce distant relapse after hepatectomy.

Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years.

BACKGROUND: This study explores whether genomic profiles of colorectal liver metastasis (CRLM) patients with early onset (EO, < 50 years old) and screening age (SA) primary diagnosis are associated with overall survival (OS). METHODS: All patients undergoing hepatectomy between 2002 and 2017 were identified and tumor specimens with next-generation sequencing data were cataloged. Gene and signaling-level alterations were checked for association with OS from primary diagnosis accommodating for left-truncated survival. RESULTS: Of 1822 patients, 333 were sequenced-127 (38%) EO-CRLM and 206 (62%) SA-CRLM patients. More aggressive features presented in EO-CRLM patients-synchronous metastatic presentation (83% vs. 75%, p < 0.001) and primary node-positive disease (71% vs. 61%, p < 0.001). The median OS from primary diagnosis was 11.8 years (95% confidence interval = 7.94-NA). Five-year OS did not differ by age (p = 0.702). On multivariable analysis, altered APC (EO-CRLM: [hazard ratio [HR] = 0.37, p = 0.018] vs. SA-CRLM:[HR = 0.61, p = 0.260]), BRAF (EO-CRLM:[HR = 4.38, p = 0.007] vs. SA-CRLM:[HR = 4.78, p = 0.032]), and RAS-TP53 (EO-CRLM:[HR = 2.82, p = 0.011] vs. SA-CRLM:[HR = 2.35, p = 0.003]) associated with OS. CONCLUSIONS: Despite bearing more aggressive features, EO-CRLM patients had similar genomic profiles and survival as SA-CRLM patients. Better performance status in younger patients leading to increased treatment tolerance may partly explain this. As screening and treatment strategies from older patients are applied to younger patients, genomic predictors of biology identified historically in older cohorts could apply to EO patients.

Distinct Genomic Profiles are Associated With Conversion to Resection and Survival in Patients With Initially Unresectable Colorectal Liver Metastases Treated With Systemic and Hepatic Artery Chemotherapy.

OBJECTIVE: To examine genomic correlates of conversion to resection (CTR and overall survival (OS) in patients with initially unresectable colorectal liver metastasis (IU-CRLM) treated with combination systemic and hepatic artery infusion (HAI) chemotherapy. BACKGROUND: In patients presenting with IU-CRLM, combination systemic and HAI chemotherapy enables CTR with associated long-term OS in a subset of patients. Genomic correlates of CTR and OS in IU-CRLM have not been previously explored. METHODS: Specimens from IU-CRLM patients receiving systemic/HAI chemotherapy (2003-2017) were submitted for next-generation sequencing. Fisher Exact test assessed associations with CTR, and Kaplan-Meier/Cox methods assessed associations with OS from HAI initiation. RESULTS: Of 128 IU-CRLM patients, 51 (40%) underwent CTR at median 6 months (range: 3-35) from HAI initiation. CTR and persistently unresectable cohorts differed significantly in preoperative systemic chemotherapy exposure, node-positive primary status, and size of largest liver metastasis. Median and 5-year OS was 66 months and 51%. CTR was associated with prolonged survival (time-dependent HR 0.23,95% CI: 0.12-0.46, P < 0.001). The most frequently altered genes were APC (81%), TP53 (77%), and KRAS (37%). Oncogenic mutations in SOX9 and BRAF were associated with CTR. BRAF mutations, any RAS pathway alterations, and co-altered RAS/RAF-TP53 mutations wereassociated with worse survival. Classification and regression tree analysis defined prognostically relevant clusters of genomic risk to reveal co-altered RAS/RAF-TP53 as the highest risk subgroup. Co-altered RAS/RAF-TP53 remained independently associated with worse survival (HR 2.52, 95% CI: 1.37-4.64, P = 0.003) after controlling for CTR, number of liver metastases, and preoperative extrahepatic disease. CONCLUSIONS: Distinct genomic profiles are associated with CTR and survival in patients with IU-CRLM treated with HAI/systemic chemotherapy. Presence of SOX9, BRAF , and co-altered RAS/RAF- TP53 mutations are promising biomarkers that, when validated in larger datasets, may impact treatment of IU-CRLM patients.

Artificial intelligence for prediction of donor liver allograft steatosis and early post-transplantation graft failure.

BACKGROUND: Donor livers undergo subjective pathologist review of steatosis before transplantation to mitigate the risk for early allograft dysfunction (EAD). We developed an objective, computer vision artificial intelligence (CVAI) platform to score donor liver steatosis and compared its capability for predicting EAD against pathologist steatosis scores. METHODS: Two pathologists scored digitized donor liver biopsy slides from 2014 to 2019. We trained four CVAI platforms with 1:99 training:prediction split. Mean intersection-over-union (IU) characterized CVAI model accuracy. We defined EAD using liver function tests within 1 week of transplantation. We calculated separate EAD logistic regression models with CVAI and pathologist steatosis and compared the models' discrimination and internal calibration. RESULTS: From 90 liver biopsies, 25,494 images trained CVAI models yielding peak mean IU = 0.80. CVAI steatosis scores were lower than pathologist scores (median 3% vs 20%, P < 0.001). Among 41 transplanted grafts, 46% developed EAD. The median CVAI steatosis score was higher for those with EAD (2.9% vs 1.9%, P = 0.02). CVAI steatosis was independently associated with EAD after adjusting for donor age, donor diabetes, and MELD score (aOR = 1.34, 95%CI = 1.03-1.75, P = 0.03). CONCLUSION: The CVAI steatosis EAD model demonstrated slightly better calibration than pathologist steatosis, meriting further investigation into which modality most accurately and reliably predicts post-transplantation outcomes.

Advances in the surgical management of gastric and gastroesophageal junction cancer.

Since Theodore Billroth and Cesar Roux perfected the methods of post-gastrectomy reconstruction in the late 19th century, surgical management of gastric and gastroesophageal cancer has made incremental progress. The majority of patients with localized disease are treated with perioperative combination chemotherapy or neoadjuvant chemoradiation. Staging laparoscopy before initiation of treatment or before surgical resection has improved staging accuracy and can drastically inform treatment decisions. The longstanding and contentious debate on the optimal extent of lymph node dissection for gastric cancer appears to have settled in favor of D2 dissection with the recently published 15-year follow-up of the Dutch randomized trial. Minimally invasive gastric and gastroesophageal resections are performed routinely in most centers affording faster recovery and equivalent oncologic outcomes. Pylorus-preserving distal (central) gastrectomy has emerged as a less invasive, function-preserving option for T1N0 middle-third gastric cancers, while randomized data on its oncologic adequacy are pending. Multi-visceral resections and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has been utilized selectively for patients with locally advanced tumors who have demonstrated disease control on preoperative chemotherapy. This review summarizes the current standard of surgical care for gastroesophageal junction and gastric cancer as well as highlights recent and upcoming advances to the field.

Recurrence After Liver Resection of Colorectal Liver Metastases: Repeat Resection or Ablation Followed by Hepatic Arterial Infusion Pump Chemotherapy.

BACKGROUND: The aim of this study was to investigate the effectiveness of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after complete resection or ablation of recurrent colorectal liver metastases (CRLM). METHODS: A retrospective cohort study was conducted of patients from two centers who were treated with resection and/or ablation of recurrent CRLM only between 1992 and 2018. Overall survival (OS) and hepatic disease-free survival (hDFS) were estimated using the Kaplan-Meier method. The Cox regression method was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CI). RESULTS: Of 374 eligible patients, 81 (22%) were treated with adjuvant HAIP chemotherapy. The median follow-up for survivors was 65 months (IQR 32-118 months). Patients receiving adjuvant HAIP were more likely to have multifocal disease and receive perioperative systemic chemotherapy at time of resection for recurrence. A median hDFS of 46 months (95% CI 29-81 months) was found in patients treated with adjuvant HAIP compared with 18 months (95% CI 15-26 months) in patients treated with resection and/or ablation alone (p = 0.001). The median OS and 5-year OS were 89 months (95% CI 52-126 months) and 66%, respectively, in patients treated with adjuvant HAIP compared with 57 months (95% CI 47-67 months) and 47%, respectively, in patients treated with resection and/or ablation only (p = 0.002). Adjuvant HAIP was associated with superior hDFS (adjusted HR 0.599, 95% CI 0.38-0.93, p = 0.02) and OS (adjusted HR 0.59, 95% CI 0.38-0.92, p = 0.02) in multivariable analysis. CONCLUSION: Adjuvant HAIP chemotherapy after resection and/or ablation of recurrent CRLM is associated with superior hDFS and OS.

Extrahepatic recurrence rates in patients receiving adjuvant hepatic artery infusion and systemic chemotherapy after complete resection of colorectal liver metastases.

BACKGROUND: This study investigated the effect of the reduced dose of systemic chemotherapy (SYS) on recurrence patterns in patients receiving adjuvant hepatic artery infusion (HAI) chemotherapy after complete colorectal liver metastases (CRLM) resection. METHODS: Patients undergoing complete CRLM resection between 2000 and 2007 were selected from a prospectively maintained database and categorized as receiving SYS or HAI + SYS. Those with pre and/or intraoperative extrahepatic disease, documented death, or recurrence within 30 days of CRLM resection were excluded. Competing risk, Fine and Gray's tests were used to compare SYS versus HAI + SYS for time-to-organ recurrence. RESULTS: Of 361 study patients, 153 (42.4%) received SYS and 208 (57.6%) received HAI + SYS. The median follow-up for survivors was 100 (range = 12-185) and 156 months (range = 18-217) for SYS and HAI + SYS, respectively. The 5-year cumulative incidence (CI) of any liver recurrence was greater for those receiving SYS (SYS = 41.9% vs. HAI + SYS = 28.6%, p = .005). The 5-year CI of developing any lung or extrahepatic recurrence for SYS patients was 36.2% and 47.9% compared with 44.5% (p = .242) and 51.7% (p = .551), respectively, in patients receiving HAI + SYS. CONCLUSION: Despite the reduced dose of SYS, adjuvant HAI + SYS after CRLM resection is not associated with a significantly increased risk of extrahepatic recurrence.