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.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Thunderbeat™ Integrated Bipolar and Ultrasonic Forceps in the Whipple Procedure: A Prospective Randomized Trial.

Thunderbeat™ is a device that uses both ultrasonic and advanced bipolar energies to achieve hemostasis. It has been evaluated in a variety of clinical contexts, but no literature exists regarding its application to pancreatic surgery. Using a prospective, randomized controlled trial, we evaluated its safety and efficacy in the Whipple procedure. Thirty-two participants were enrolled in the study. The Thunderbeat™ device during the Whipple procedure showed similar safety profile compared to standard of care.

Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions.

BACKGROUND: Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable. METHODS: Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015). RESULTS: The SL utilization rate increased over time and was significantly higher in GBC than DC and HC. SL yield was 16.8% and did not differ between groups or over time. In patients undergoing attempted resection with prior SL, the curative resection rate did not differ between subtypes. In patients undergoing attempted resection without prior SL, the curative resection rate was less in GBC compared with DC or HC. After matching cohorts by inverse probability weighting, prior SL was associated with curative resection in GBC only (odds ratio [OR], 2.41, 95% CI, 1.36-4.27). On multivariable regression analysis, elevated carbohydrate antigen 19-9 (CA 19-9), low serum albumin, and GBC were strong predictors of distant disease on SL. After categorizing patients undergoing SL into low, intermediate, and high-risk groups based on these parameters, SL yield improved progressively from 10.0% to 19.6% to 52.6%. CONCLUSIONS: We recommend routine SL for patients with GBC, particularly with elevated CA19-9 level and/or decreased serum albumin.

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.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy. METHODS: Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival. RESULTS: In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323). CONCLUSION: The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.

Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival.

BACKGROUND AND OBJECTIVES: The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD). METHODS: Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients. RESULTS: The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.

Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

BACKGROUND: Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection. METHODS: We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. RESULTS: A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded. CONCLUSIONS: AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.

Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection. METHODS: A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late. RESULTS: With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence. CONCLUSIONS: Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.

Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium.

BACKGROUND: Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined. METHODS: Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed. RESULTS: Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS. CONCLUSION: In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics.

Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%). CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. METHODS: All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). RESULTS: Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. CONCLUSIONS: By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

Surgery for lymph node metastases of medullary thyroid carcinoma: A review.

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease.

Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients With Early Stage Breast Cancer.

OBJECTIVE: Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. BACKGROUND: Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1-T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. METHODS: Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by 2 independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. RESULTS: A total of 647 patients with clinical T1-T2, N0 breast cancer underwent AUS between January 2008 and March 2013. AUS had a sensitivity of 70%, NPV of 84%, and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (>2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. CONCLUSIONS: AUS accurately excludes clinically significant ALN disease in patients with clinical T1-T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients, where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions.

Is Linitis Plastica a Contraindication for Surgical Resection: A Multi-Institution Study of the U.S. Gastric Cancer Collaborative.

BACKGROUND: Current staging and treatment guidelines for gastric adenocarcinoma do not differentiate between linitis plastic (LP) and non-LP cancers. Significant controversy exists regarding the surgical management of LP patients. METHODS: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 gastric cancer patients who underwent resection between 2000 and 2012 were identified. Clinicopathologic and outcomes data of 58 LP patients were compared to 811 non-LP patients. RESULTS: Stage III/IV disease was more common at presentation in LP patients compared with non-LP patients (90 vs. 44 %, p < 0.01). Despite the fact that most LP patients underwent total gastrectomy (88 vs. 39 %, p < 0.01), final positive margins were more common in LP patients (33 vs. 7 %, p < 0.01). The use of frozen section allowed 15 intraoperative positive margins in 38 patients to be converted to negative final margins. Median overall survival (OS) was significantly worse in patients with LP (11.6 vs. 37.8 months, p < 0.01). There was no difference in median OS of LP patients based on stage (I/II, 17.3 mo; III, 10.6 mo; IV, 12.0 mo; p = 0.46). LP and non-LP patients who underwent optimal resection (negative margin and D2/3 lymphadenectomy) had better survival compared with those with nonoptimal resections. The median OS for optimally resected stage III LP (n = 22) and stage III non-LP (n = 185) patients was nearly identical (26.7 vs. 25.3 mo; p = 0.69). CONCLUSIONS: Future staging systems and treatment guidelines should differentiate between LP and non-LP gastric cancers. Long-term survival in select LP patients who undergo optimal resections is comparable to optimally resected non-LP patients.

Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the U.S. Gastric Cancer Collaborative.

BACKGROUND: Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. METHODS: We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. RESULTS: Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). CONCLUSIONS: Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma.

BACKGROUND: Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). METHODS: Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). RESULTS: Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034). CONCLUSIONS: Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.

Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC. METHODS: Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. RESULTS: A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01). CONCLUSIONS: Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.

Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes.

BACKGROUND: The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC. METHODS: A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1. RESULTS: R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04). CONCLUSIONS: A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.