Factors Associated with Early Discharge after Non-Emergent Right Colectomy for Colon Cancer: A NSQIP Analysis.

The National Surgical Quality Improvement Project (NSQIP) dataset was used to identify perioperative variables associated with the length of stay (LOS) and early discharge among cancer patients undergoing colectomy. Patients who underwent non-emergent right colectomy for colon cancer from 2012 to 2019 were identified from the NSQIP and colectomy-targeted databases. Postoperative LOS was analyzed based on postoperative day (POD) of discharge, with patients grouped into Early Discharge (POD 0-2), Standard Discharge (POD 3-5), or Late Discharge (POD ≥ 6) cohorts. Multivariable ordinal logistic regression was performed to identify risk factors associated with early discharge. The NSQIP query yielded 26,072 patients: 3684 (14%) in the Early Discharge, 13,414 (52%) in the Standard Discharge, and 8974 (34%) in the Late Discharge cohorts. The median LOS was 4.0 days (IQR: 3.0-7.0). Thirty-day readmission rates were 7% for Early Discharge, 8% for Standard Discharge, and 12% for Late Discharge. On multivariable regression analysis, risk factors significantly associated with a shorter LOS included independent functional status, minimally invasive approach, and absence of ostomy or additional bowel resection (all p < 0.001). Perioperative variables can be used to develop a model to identify patients eligible for early discharge after right colectomy for colon cancer. Efforts to decrease the overall median length of stay should focus on optimization of modifiable risk factors.

Swallowing dysfunction after minimally invasive oesophagectomy.

OBJECTIVES: Patients undergoing oesophagectomy frequently experience malnutrition, which in combination with the catabolic effects of surgery can result in loss of muscle mass and function. Safe swallowing requires preservation of muscle mass. Swallowing dysfunction puts postoperative patients at risk for aspiration and pneumonia. Modified Barium Swallow Study (MBSS) enables assessment of postoperative swallowing impairments. The current study assessed incidence and risk factors associated with swallowing dysfunction and restricted diet at discharge in patients after oesophagectomy in a high-volume surgical centre. METHODS: Patients with an MBSS after oesophagectomy were identified between March 2015 to April 2020 at a high-volume surgical centre. Swallowing was quantitatively evaluated on MBSS with the Rosenbek Penetration-Aspiration Scale (PAS). Muscle loss was evaluated clinically with preoperative hand grip strength (HGS). Univariable and multivariable logistic and linear regression analyses were performed. RESULTS: 129 patients (87% male; median age 66 years) underwent oesophagectomy with postoperative MBSS. Univariate analysis revealed older age, preoperative feeding tube, lower preoperative HGS and discharge to non-home were associated with aspiration or penetration on MBSS. Age and preoperative feeding tube remained as independent predictors in the multivariable analysis. Both univariate and multivariable analyses revealed increased age and preoperative feeding tube were associated with diet restrictions at discharge. CONCLUSIONS: Swallowing dysfunction after oesophagectomy is correlated with increased age and need for preoperative enteral feeding tube placement. Further research is needed to understand the relationship between muscle loss and aspiration with the goal of enabling preoperative physiological optimisation and patient selection.

Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer.

BACKGROUND: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer. METHODS: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools. RESULTS: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p < 0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p < 0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74). CONCLUSIONS: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation.

A multi-institutional validation study of prognostic nomograms for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection. METHODS: Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index). RESULTS: Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability. CONCLUSIONS: In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.

Modern multimodality management of patients with caval leiomyosarcoma: New treatment paradigms and potential molecular insights.

BACKGROUND AND OBJECTIVES: Caval leiomyosarcomas (cLMS) are rare soft tissue sarcomas historically associated with high recurrence rates and poor prognosis. While radical resection remains the mainstay of therapy for cLMS, new systemic therapies have presented opportunities for multimodality treatment. We examined the clinical outcomes of patients with cLMS treated with modern, multimodality approaches, and compared their outcomes to those of patients with noncaval retroperitoneal LMS (ncLMS). METHODS: A retrospective, single-institution review identified all patients diagnosed with primary retroperitoneal LMS from 2012 to 2018. Radiographic and pathologic review distinguished patients with cLMS and ncLMS. Standard clinicopathologic variables and response to chemotherapy (when applicable) were analyzed. Primary endpoints were overall (OS) and progression-free survival (PFS). RESULTS: Eleven patients with cLMS were identified. Median tumor size was 7.5 cm (IQR, 5.0-14.3 cm); all patients had Stage II/III disease. Seven patients received neoadjuvant chemotherapy. Nine cLMS patients underwent R0/R1 resection; two did not complete resection. Six patients received adjuvant systemic therapy. Twenty patients with ncLMS were treated during the same period. No statistical intergroup differences were noted in tumor size, pathologic grade, stage, or resection margin status. Patients with ncLMS were less likely to receive neoadjuvant (10% vs. 64%) and adjuvant chemotherapy (30% vs. 55%). Two-year OS (81% vs. 78%; p = NS) and PFS (55% vs. 46%; p = NS) were comparable between cLMS and ncLMS patients. CONCLUSIONS: Multimodality treatment with systemic therapy and aggressive surgical resection may achieve equivalent survival outcomes for patients with cLMS versus similar ncLMS. We recommend that all patients with cLMS be evaluated for multidisciplinary treatment. Genomic and proteomic expression profiling may identify novel or targetable mutations.

Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors.

OBJECTIVES: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. METHODS: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. RESULTS: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. CONCLUSIONS: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas.

BACKGROUND: In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers. METHODS: The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS. RESULTS: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23). CONCLUSIONS: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.

Imaging or Fiber Probe-Based Approach? Assessing Different Methods to Detect Near Infrared Autofluorescence for Intraoperative Parathyroid Identification.

BACKGROUND: Near infrared autofluorescence (NIRAF) can guide intraoperative parathyroid gland (PG) identification. NIRAF detection devices typically rely on imaging and fiber probe-based approaches. Imaging modalities provide NIRAF pictures on adjacent display monitors, and fiber probe-based systems measure tissue NIRAF and provide real-time quantitative information to objectively aid PG identification. Both device types recently gained FDA approval for PG identification but have never been compared directly. STUDY DESIGN: Patients undergoing thyroidectomy and/or parathyroidectomy were recruited prospectively. Target tissues were intraoperatively visualized with PDE-Neo II (imaging-based) and concurrently assessed with PTeye (fiber probe-based). For PDE-Neo II, NIRAF images were collected from in situ or excised tissues, alongside the surgeon's interpretation of visualized tissues, and retrospectively analyzed in a blinded fashion. The PTeye was concomitantly used to record NIRAF intensities and ratios from the same tissues in real time. RESULTS: Twenty patients were enrolled for concurrent evaluation with both systems, which included 33 PGs and 19 nonparathyroid sites. NIRAF imaging demonstrated 90.9% sensitivity, 73.7% specificity, and 84.6% accuracy for PG identification when interpreted in real time by the surgeon compared with 81.8% sensitivity, 73.7% specificity, and 78.8% accuracy where images were quantitatively analyzed post hoc by an independent observer. In parallel, NIRAF detection with PTeye yielded 97.0% sensitivity, 84.2% specificity, and 92.3% accuracy in real time for the same specimens. CONCLUSIONS: Both NIRAF-based systems were beneficial for identifying PGs intraoperatively. Although NIRAF imaging provides valuable spatial information to localize PGs, NIRAF detection with fiber probe provides real-time quantitative information to identify PGs in presence of ambient room lights.

Intraoperative Autofluorescence Parathyroid Identification in Patients With Multiple Endocrine Neoplasia Type 1.

IMPORTANCE: Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland enables intraoperative gland identification without the need for contrast agent injection. However, whether real-time autofluorescence imaging is useful in patients with multiple endocrine neoplasia type 1 (MEN1) and primary hyperparathyroidism is unknown. OBJECTIVE: To compare quantified intraoperative parathyroid autofluorescence imaging results for patients with MEN1-associated vs those with non-MEN1 sporadic primary hyperparathyroidism. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of prospectively collected data on a cohort of 71 consecutive patients undergoing surgery for primary hyperparathyroidism by 2 experienced endocrine surgeons between June 1, 2017, and July 31, 2018, was conducted. Intraoperative imaging was performed with a handheld NIR autofluorescence device and images were captured for analysis. Post hoc blinded imaging analysis was conducted with Image J software to quantify representative areas of greatest autofluorescence from the parathyroid, thyroid, and adjacent soft tissue. MAIN OUTCOMES AND MEASURES: Primary end points were parathyroid autofluorescence and background thyroid and soft tissue autofluorescence, reported as median values with interquartile ranges. Rates of false-negative (lack of significant parathyroid gland autofluorescence compared with background autofluorescence, defined as parathyroid autofluorescence-background autofluorescence ratio <1.10) and false-positive autofluorescence (aberrant autofluorescence of nonparathyroid tissue confirmed by pathologic testing) were analyzed. RESULTS: Of the 71 consecutive patients with primary hyperparathyroidism who underwent parathyroidectomy during the study period, 6 patients had genetically or clinically diagnosed MEN1 and 65 had sporadic non-MEN1 hyperparathyroidism. Most patients were women (MEN1: 4 [67%]; non-MEN1: 51 [78%]). Median (interquartile range) age was 49.0 (38.0-53.8) years in the MEN1 cohort and 61.0 (54.0-67.0) years in the non-MEN1 cohort. No clinically significant differences in serum preoperative parathyroid hormone level or parathyroid gland size or weight on pathologic examination were observed between the 2 cohorts. The median absolute value of in situ parathyroid autofluorescence was significantly lower in the MEN1 cohort than the non-MEN1 cohort (54.4 vs 74.3; Hedges g = -1.03; 95% CI, -1.89 to -0.17), as was the ratio of parathyroid to background autofluorescence (1.08 vs 1.59; g = -1.59; 95% CI, -2.23 to -0.96). Three patients (50%) with MEN1 had false-negative nonfluorescent parathyroid adenomas vs 6 patients (9%) without MEN1. Nonparathyroid fibroadipose tissue of patients with MEN1 exhibited greater background autofluorescence, leading to high false-positive rates (5 of 6 patients [83%]) vs only 3 of 65 (5%) false-positive autofluorescence nonparathyroid specimens among patients without MEN1. CONCLUSIONS AND RELEVANCE: Intraoperative identification of parathyroid glands using their autofluorescence by real-time NIR imaging appears to have utility in patients with primary hyperparathyroidism. In this initial cohort of patients with MEN1, decreased parathyroid autofluorescence and increased background autofluorescence of nonparathyroid tissue may be associated with high rates of false-negative and false-positive fluorescence, potentially limiting the utility of this adjunct in this specific subset of patients.

Intraoperative Parathyroid Autofluorescence Detection in Patients with Primary Hyperparathyroidism.

BACKGROUND: Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland may improve intraoperative gland identification without the need for contrast agent injection. Compared with patients undergoing surgery for thyroid disease, identification of pathologic parathyroid tissue in patients with hyperparathyroidism is essential. This study analyzed the utility of a novel real-time autofluorescence imaging system in patients with primary hyperparathyroidism enrolled in a prospective feasibility clinical trial. METHODS: Data on patients undergoing surgery for primary hyperparathyroidism by two experienced endocrine surgeons were prospectively collected. Intraoperative imaging was performed with a handheld NIR device, and images were captured for analysis. The collected data included the surgeon's confidence in parathyroid identification, both with ambient light and use of NIR imaging, as well as how the imaging affected the surgical procedure. Images were quantified by Image J software, with autofluorescence reported as mean values ± SD. RESULTS: From 2017 to 2018, 59 consecutive patients with a diagnosis of primary hyperparathyroidism underwent resection of 69 parathyroid glands. Use of NIR imaging increased the intraoperative confidence of parathyroid identification (on a scale of 0-5) from an average of 4.1 to an average of 4.4 (+0.3, p = 0.003), all of which were confirmed pathologically. The addition of autofluorescence helped to identify the parathyroid gland in 12 patients (20%), and to rule out other soft tissue as not parathyroid in an additional 9 patients (15%). The mean autofluorescence for the parathyroid in situ (75.9 ± 21.3) was significantly greater than that for the thyroid (61.1 ± 17.4) or soft tissue (53.3 ± 19.2) (p < 0.001 for both). The mean absolute difference in parathyroid versus background thyroid autofluorescence was +15.2 (range, 2.4-53.1). CONCLUSION: This is the first prospective trial to examine the utility of parathyroid autofluorescence for identifying glands exclusively in patients with parathyroid disease. Intraoperative identification and localization of parathyroid glands by real-time, NIR imaging using their intrinsic autofluorescence is feasible and may provide a useful adjunct during parathyroid surgery.

Challenges of surgical management of intrahepatic cholangiocarcinoma.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy arising from biliary tract epithelium within bile ducts proximal to the secondary biliary radicles. The majority of patients are diagnosed with locally advanced or metastatic disease at presentation. Surgical resection remains the only potentially curative option, but poses unique challenges due to the large size and aggressive behavior of these tumors. Areas covered: The goal of surgical management of iCCA is margin negative (R0) hepatic resection with preservation of adequate size liver remnant and function. Data regarding role of staging laparoscopy, margin status, portal lymphadenectomy, and vascular resection for iCCA are reviewed. Perioperative systemic therapy may have value, although prospective data have been lacking. Recurrence rates remain high even after R0 resection; among patients with recurrent disease limited to the liver, re-resection or locoregional therapies may play a role. Liver transplantation may be an option for select patients with very early-stage iCCA, although this should be done on a protocol-only basis. Expert commentary: Appropriate preoperative patient selection and surgical technique are paramount to ensure optimal oncologic outcomes for patients with resectable iCCA. Improving systemic and locoregional therapy options may help decrease recurrence rates and improve long-term survival for this aggressive malignancy.

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

BACKGROUND: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA. METHODS: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status. RESULTS: Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829). CONCLUSIONS: Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

Clinicopathologic score predicting lymph node metastasis in T1 gastric cancer.

BACKGROUND: Although gastrectomy with adequate regional nodal examination is considered the standard of care for invasive gastric adenocarcinoma, endoscopic resection has been adopted increasingly in select patients with T1 gastric cancer. The objective of this study was to identify preoperative predictors of lymph node metastasis in patients in the United States with T1 gastric cancer. METHODS: Patients who underwent operative resection for T1 gastric cancer between 2000 and 2012 were identified from a multi-institutional database. Clinicopathologic predictors of lymph node metastasis were determined using univariate and multivariate logistic regression. A preoperative score was created, assigning points based on each variable's regression coefficient. RESULTS: Among 835 patients with gastric cancer undergoing curative-intent surgical resection, 176 patients (20.5%) had T1 disease confirmed on final pathology. Of those, 38 patients (22%) had lymph node metastasis. Independent predictors of lymph node involvement on multivariate analysis were poor differentiation, T1b stage, lymphovascular invasion, and tumor size >2 cm. A clinicopathologic risk score composed of these 4 variables was created. Receiver operating curve analysis showed excellent discrimination (area under the curve = 0.79) and 100% sensitivity in detecting lymph node metastasis when only one of the aforementioned factors was present. CONCLUSIONS: In this cohort of U.S. patients with T1 gastric adenocarcinoma, the lack of lymph node involvement could be predicted by the absence of several unfavorable factors, including T stage, poor differentiation, lymphovascular invasion, and size >2 cm.

The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma.

BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. METHODS: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable." CONCLUSION: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.

Hepatobiliary Mucinous Cystic Neoplasms With Ovarian Type Stroma (So-Called "Hepatobiliary Cystadenoma/Cystadenocarcinoma"): Clinicopathologic Analysis of 36 Cases Illustrates Rarity of Carcinomatous Change.

The literature is highly conflicting on hepatobiliary mucinous cystic neoplasms (MCNs), aka "hepatobiliary cystadenoma/cystadenocarcinoma," largely because ovarian stroma (OS) was not a requirement until WHO-2010 and is not widely applied even today. In this study, MCNs (with OS) accounted for 24 of 229 (11%) resected hepatic cysts in one institution. Eight of the 32 (25%) cysts that had been originally designated as hepatobiliary cystadenoma/cystadenocarcinoma at the time of diagnosis proved not to have an OS during this review and were thus re-classified as non-MCN. In total, 36 MCNs (with OS) were analyzed-24 from the institutional files and 12 consultation cases. All were women. Mean age was 51 (28 to 76 y). Mean size was 11 cm (5 to 23 cm). Most (91%) were intrahepatic and in the left lobe (72%). Preoperative imaging mentioned "neoplasm" in 14 (47%) and carcinoma was a differential in 6 (19%) but only 2 proved to have carcinoma. Microscopically, only 47% demonstrated diffuse OS (>75% of the cyst wall/lining); OS was often focal. The cyst lining was often composed of non-mucinous biliary epithelium, and this was predominant in 50% of the cases. Degenerative changes of variable amount were seen in most cases. In situ and invasive carcinoma was seen in only 2 cases (6%), both with small invasion (7 and 8 mm). Five cases had persistence/recurrence, 2 confirmed operatively (at 7 mo and 15 y). Of the 2 cases with carcinoma, one had "residual cyst or hematoma" by radiology at 4 months, and the other was without disease at 3 years. In conclusion, many cysts (25%) previously reported as hepatobiliary cystadenoma/cystadenocarcinoma are not MCNs. True MCNs are uncommon among resected hepatic cysts (11%), occur exclusively in females, are large, mostly intrahepatic and in the left lobe (72%). Invasive carcinomas are small and uncommon (6%) compared with their pancreatic counterpart (16%). Recurrences are not uncommon following incomplete excision.

Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy.

BACKGROUND: The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer. METHODS: Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated. RESULTS: Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05). CONCLUSION: Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).

A Multi-Institutional Study Comparing the Use of the American Joint Committee on Cancer 7th Edition Esophageal versus Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population.

Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by T or N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.

Post-hepatectomy hyperbilirubinemia: The point of no return.

BACKGROUND: Post-hepatectomy hyperbilirubinemia is associated with liver insufficiency and failure. The highest survivable peak total bilirubin (ptbili) is not defined. This study aimed to identify the postop ptbili beyond which survival is improbable or impossible. METHODS: An institutional database of major hepatectomies (≥3 segments, no biliary resections), 2000-2012 was reviewed. Data were analyzed to find ptbili in the first 45 postop days. Factors associated with 90-day mortality (90 DM) and those predictive of ptbili were determined. RESULTS: 603 pts were analyzed with 90DM of 4.5%. 90 DM for a ptbili ≥ 18 (n = 15) was 86.6%, but only 2.5% for a ptbili < 18. All 6 pts with a ptbili ≥ 30 died. On multivariate analysis, postop ptbili ≥ 18 (HR34.95, CI 3.8-324; p = 0.002) and cirrhosis (HR6.4, CI 1.2-33.2; p = 0.027) were associated with 90DM. Factors associated with a ptbili ≥ 18 were age >65 (HR14.24, CI 2.9-70.5; p = 0.001), preop chemotherapy (HR4.77, CI 1.3-18.2; p = 0.02) and postop FFP (HR12.5, CI 2.6-56.2; p = 0.001). CONCLUSION: Postop ptbili ≥ 18 after major hepatectomy has an 86.6% risk of 90DM; there are no survivors for tbili ≥ 30. These values may guide postop counseling for prognosis. Future studies may evaluate tbili ≥ 18 as an indication for hepatic replacement therapy.