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Background Cholecystectomy in patients with hematologic malignancies remains poorly understood. Methods We retrospectively evaluated patients with hematologic malignancies who underwent cholecystectomy at a single institution. Results Of 313 patients who presented for evaluation of abdominal pain, 64 underwent cholecystectomy for acute cholecystitis (34.4%), gangrenous cholecystitis (21.9%), chronic cholecystitis (23.4%), and cholelithiasis (20%). Most had a history of hematopoietic cell transplantation (62.5%) and/or immunosuppressive medication within 30 days of consultation (82.8%). Ultrasound had a 39% false-negative rate for acute nongangrenous cholecystitis. Operative time was 92 ± 39 min, 7 were performed open, 10 had intraoperative transfusions, and 4 had grade 3+ complications. Intraoperative transfusion was associated with increased postoperative length of stay (p = 0.03). Open procedure, operative time, estimated blood loss, intraoperative transfusion, and complications were not associated with timing of surgery. Conclusions Patients with hematologic malignancies can safely undergo cholecystectomy. Length of postoperative stay for inpatients is associated with intraoperative blood transfusion.

Background Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status. Methods A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS. Results 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection. Discussion In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.

BACKGROUND: Surgical resection for sarcoma lung metastases has been associated with improved overall survival (OS). METHODS: Patients who underwent curative-intent resection of sarcoma lung metastases (2000–2016) were identified from the US Sarcoma Collaborative. Patients with extrapulmonary metastatic disease or R2 resections of primary tumor or metastases were excluded. Primary endpoint was OS. RESULTS: Three hundred and fifty-two patients met inclusion criteria. Location of primary tumor was truncal/extremity in 85% (n = 270) and retroperitoneal in 15% (n = 49). Forty-nine percent (n = 171) of patients had solitary and 51% (n = 180) had multiple lung metastasis. Median OS was 49 months; 5-year OS 42%. Age ≥55 (HR 1.77), retroperitoneal primary (HR 1.67), R1 resection of primary (HR 1.72), and multiple (≥2) lung metastases (HR 1.77) were associated with decreased OS(all p < 0.05). Assigning one point for each factor, we developed a risk score from 0 to 4. Patients were then divided into two risk groups: low (0–1 factor) and high (2–4 factors). The low-risk group (n = 159) had significantly better 5-year OS compared to the high-risk group (n = 108) (51% vs. 16%, p < 0.001). CONCLUSION: We identified four characteristics that in aggregate portend a worse OS and created a novel prognostic risk score for patients with sarcoma lung metastases. Given that patients in the high-risk group have a projected OS of

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.

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. 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. 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. 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.

Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis.A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P.001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P.001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P.001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22).Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.

Pancreatectomy results in significant postoperative pain and typically requires opioid analgesia for adequate pain control. Local anesthetics may decrease postoperative pain and opioid requirements but can be limited by onset of action, duration of effect, and inability to titrate dosing after administration. This can be overcome by surgeon placement of tunneled peri-incisional catheters with continuous wound infusion (CWI). This retrospective cohort study analyzed patients undergoing open pancreatic tumor resection. All the patients received patient-controlled analgesia (PCA), enabling an objective comparison of opioid requirements, and underwent the same recovery pathway. The patients received CWI (n = 45), PCA alone (n = 11), or epidural analgesia (EA) (n = 9). The primary outcome was total opioid use in terms of intravenous morphine milligram equivalents (MMEs) and patient-reported pain scores on a numeric rating scale (NRS) of 0 to 10. No differences in baseline patient or tumor characteristics were observed. In both the uni- and multivariate analyses, CWI was associated with lower opioid use than PCA (MME, 83 vs 207 mg; p = 0.004) or EA (MME, 83 vs 156 mg; p

Background/objective Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS). Methods Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS). Results Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation. Conclusions In our cohort, patients with LMS have a low local recurrence rate (12–15%) and modest distant recurrence rate (29–35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

BACKGROUND The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data. METHODS All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed. RESULTS Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size

BACKGROUND AND OBJECTIVES Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas. MATERIALS AND METHODS A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed. RESULTS A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P

OBJECTIVE To evaluate patient satisfaction scores as a function of physician and patient race and sex. BACKGROUND Patient satisfaction is increasingly used as a surrogate for physician performance. How patient and surgeon race and ethnicity affect perceptions of surgeon communication and care is not widely explored. METHODS Press Ganey patient satisfaction surveys collected from January 2019 to September 2020 were studied. Multivariate logistic regressions were used to identify factors associated with favorable surgeon performance as a function of patient and surgeon demographics. RESULTS A total of 4732 unique outpatient satisfaction survey responses were analyzed. The majority of patients were White (60.5%), followed by Asian (8.6%), Black (4.2%), and Hispanic (4.3%). URM accounted for 8.9% of the 79 surgeons evaluated, and 34% were female. Black, Hispanic, and Asian patients were more likely to report unfavorable experiences than their White counterparts (P < 0.01). Spanish-speaking patients were most likely to perceive that surgeon show less respect for patient concerns (13.9% vs 9.3%, P = 0.004) and inadequate time spent explaining health concerns (12.6% vs 9.2%, P < 0.001). Female surgeons were more likely to achieve the highest overall ratings for effective communication, whereas Asian surgeons received lower scores. Asian surgeons were more likely than non-Asian surgeons to receive lower scores in explanation (37.3% vs 44.1%, P = 0.003). After adjusting for confounding factors, Asian surgeons had 26% lower odds of receiving favorable scores for overall communication (odds ratio: 0.736, 95% confidence interval: 0.619-0.877, P = 0.001). CONCLUSIONS Both patient and surgeon race and sex drive negative perceptions of patient-physician communication. As URM report more negative experiences, further studies should focus on effects of surgeon cultural awareness on underrepresented patient satisfaction.

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.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.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).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.

BACKGROUND: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures. QUESTIONS/PURPOSES: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma? METHODS: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher’s exact tests for categorical predictors, and Wilcoxon’s rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot. RESULTS: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%]). CONCLUSIONS: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications. LEVEL OF EVIDENCE: Level III, therapeutic study.

BACKGROUND. Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known. METHODS. All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS). RESULTS. Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p = 0.034) and major complications (46 vs 16%; p < 0.001). Transfusion was associated with worse median RFS (19 vs 32 months; p = 0.006) and OS (15 vs 29 months; p = 0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1–3.0; p = 0.031] and OS (HR 1.9; 95% CI 1.1–3.3; p = 0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of ≥ 2 pRBCs was associated with lower RFS (17 vs 32 months; p < 0.001) and OS (14 vs 29 months; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4–4.5; p = 0.001) and OS (HR 4.0; 95% CI 2.2–7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused. CONCLUSION. Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as ≥ 2 units.

Background & Aims Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. Methods On March 5–6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. Results The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. Conclusions There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.

BACKGROUND: Nephrectomy is often required during en bloc resection of a retroperitoneal sarcoma (RPS) to achieve an R0/R1 resection. The impact of nephrectomy on postoperative renal function in this patient population, who may also benefit from subsequent nephrotoxic systemic therapy, is not well described. METHODS: The United States Sarcoma Collaborative (USSC) database was queried for patients undergoing RPS resection between 2000–2016. Patients missing pre- or postoperative measures of renal function were excluded. A matched cohort was created using coarsened exact matching. Weighted logistic regression was used to further control for differences in the nephrectomy vs non-nephrectomy cohorts. Primary outcomes included postoperative acute kidney injury (AKI), acute renal failure (ARF), and dialysis. RESULTS: The initial cohort consisted of 858 patients, of which 3 patients (0.3%) required postoperative dialysis. The matched cohort consisted of 411 patients of which 108 patients (26%) underwent nephrectomy. Patients that underwent nephrectomy had higher rates of postoperative AKI (14.8% vs 4.3%, p

The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied.Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70 y, n = 171) and nonelderly (70 y, n = 494) patients.There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P = 0.401 and 18% versus 17%; P = 0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7 d interquartile range [IQR: 5-9] versus 6 d [IQR: 4-9], P = 0.528 and 11% versus 12%, P = 0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P 0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P = 0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P 0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes.Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology.

The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously. Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5 years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5 years were excluded from the study. The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5 years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P = 0.008) and a lower rate of lymph node involvement (42% vs. 15%; P = 0.027) and R1 margins (39% vs. 17%; P = 0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups. One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).

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.

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.

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. 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. 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

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) 51.0–2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7–5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5–4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1–3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1–12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9–6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Peri-operative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.

Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P

BACKGROUND Current data on the utility of port-site excision (PSE) during re-resection for incidentally discovered gallbladder cancer (IGBC) in the US are conflicting and limited to single-institution series. METHODS All patients with IGBC who underwent curative re-resection at 10 institutions from 2000 to 2015 were included. Patients with and without PSE were compared. Primary outcome was overall survival (OS). RESULTS Of 449 pts with GBC, 266 were incidentally discovered, of which 193(73%) underwent curative re-resection and had port-site data; 47 pts(24%) underwent PSE, 146(76%) did not. The PSE rate remained similar over time (2000-2004: 33%; 2005-2009: 22%; 2010-2015:22%; P = 0.36). Both groups had similar demographics, operative procedures, and post-operative complications. There was no difference in T-stage (T1: 9 vs. 11%; T2: 52 vs. 52%; T3: 39 vs. 38%; P = 0.96) or LN involvement (36 vs. 41%; P = 0.7) between groups. A 3-year OS was similar between PSE and no PSE groups (65 vs. 43%; P = 0.07). On univariable analysis, residual disease at re-resection (HR = 2.1, 95% CI 1.4-3.3; P = 0.001), high tumor grade, and advanced T-stage were associated with decreased OS. Only grade and T-stage, but not PSE, persisted on multivariable analysis. Distant disease recurrence-rate was identical between PSE and no PSE groups (80 vs. 81%; P = 1.0). CONCLUSION Port-site excision during re-resection for IGBC is not associated with improved overall survival and has the same distant disease recurrence compared to no port-site excision. Routine port-site excision is not recommended.

Advancements in surgical technique, imaging, perioperative care, and systemic chemotherapy have improved survival for colorectal liver metastasis; however, long-term survival and curative therapies have remained largely elusive. Immunotherapy is a promising and innovative strategy in the treatment of multiple malignancies, and there is evidence to support its use in metastatic colorectal cancer. Emerging therapeutic approaches and data suggest that immunotherapy may be effective in improving outcomes for select patients with metastatic colorectal cancer to the liver.

BACKGROUND AND OBJECTIVES: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival. METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000–2016 at eight institutions of the US Sarcoma Collaborative were evaluated. RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1–8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years. CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.

The role of neoadjuvant chemotherapy (NCT) for high-risk soft tissue sarcoma (STS) is questioned. This study aimed to define which patients may experience a survival advantage with NCT. All the patients from the U.S. Sarcoma Collaborative database (2000–2016) who underwent curative-intent resection of high-grade, primary truncal/extremity STS size 5 cm or larger were included in this study. The primary end points were recurrence-free survival (RFS) and overall survival (OS). Of the 4153 patients, 770 were included in the study. The median tumor size was 10 cm, and 669 of the patients (87%) had extremity tumors. The most common histology was undifferentiated pleomorphic sarcoma (UPS), found in 42% of the patients. Of the 770 patients, 216 (28%) received NCT. The patients who received NCT had deeper, larger tumors (p

Background and objectives Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR). Methods From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups. Results LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P 1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively). Conclusions RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.

This study examined aspects of clinicians’ work environment that facilitated sustained use of prolonged exposure (PE) therapy. Surveys were completed by 566 U.S. Department of Veterans Affairs clinicians 6 and 18 months after intensive training in PE. The number of patients treated with PE at 18 months (reach) was modeled as a function of clinician demographics, clinician beliefs about PE, and work context factors. There were 342 clinicians (60.4%) who used PE at 6 and 18 months after training, 58 (10.2%) who used PE at 18 but not 6 months, 95 (16.7%) who used PE at 6 but not 18 months, and 71 (12.5%) who never adopted PE. Median reach was 12% of clinicians’ appointments with patients with posttraumatic stress disorder. Reach was predicted by flow of interested patients (incident response ratio [IRR] = 1.21 to 1.51), PE's perceived effectiveness (IRR = 1.04 to 1.31), working in a PTSD specialty clinic (IRR = 1.06 to 1.26), seeing more patients weekly (IRR = 1.04 to 1.25), and seeing fewer patients in groups (IRR = 0.83 to 0.99). Most clinicians trained in PE sustained use of the treatment, but on a limited basis. Strategies to increase reach of PE should address organizational barriers and patient engagement.

Surgical site infections (SSI) are one of the most common complications after hepato-pancreato-biliary surgery. Infectious complications may lead to an associated immune-modulatory effect that inhibits the body’s response to cancer surveillance. We sought to define the impact of SSI on long-term prognosis of patients undergoing surgical resection of extrahepatic biliary malignancies (EHBM). Patients undergoing surgery for EHBM between 2000 and 2014 were identified using a large, multi-center, national cohort dataset. Recurrence free survival (RFS) was calculated and a multivariable Cox proportional hazards model was utilized to identify potential risk factors for RFS including SSI. Seven hundred twenty-eight patients included in the analytic cohort; 236 (32.4%) patients had perihilar cholangiocarcinoma, 241 (33.1%) gallbladder cancer, and 251 (34.5%) distal cholangiocarcinoma. A major resection, liver resection, was performed in 205 (28.3%) patients, while 110 (15.2%) patients had a pancreaticoduodenectomy. The overall incidence of morbidity was 55.8%; among the 397 patients who experienced a complication, 161 patients specifically had an SSI. The SSI occurred as an infection of the surgical site (n = 70, 9.6%) or formation of an abscess in the operative bed (n = 91, 12.5%). SSI was associated with long-term survival as patients who experienced an SSI had a median RFS of 19.5 months compared with 30.5 months for those patients who did not have an SSI (HR 1.40, 95% CI 1.08–1.80; p = 0.01). Among 279 patients who had EHBM that had no associated lymph node metastases, well-to-moderate tumor differentiation, as well as an R0 resection margin, SSI remained associated with worse RFS (HR 1.84, 95% CI 1.03–3.29; p = 0.038), as well as overall survival (HR 1.87, 95% CI 1.18–2.97; p = 0.008). SSI was a relatively common occurrence following surgery for EHBM as 1 in 10 patients experienced an SSI. In addition to standard tumor-specific factors, the occurrence of postoperative SSI was adversely associated with long-term survival.

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. 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). 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. 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.

Background and objectivesMinimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery.MethodsRetrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA.ResultsA total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3%, MIS, vs. 30.9%, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p

Author(s): Tran, Thuy B; Postlewait, Lauren M; Maithel, Shishir K; Prescott, Jason D; Wang, Tracy S; Glenn, Jason; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Hatzaras, Ioannis; Shenoy, Rivfka; Pawlik, Timothy M; Norton, Jeffrey A; Poultsides, George A | Abstract: BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported.MethodPatients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded.ResultsAmong the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P l 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence.ConclusionSurgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. J. Surg. Oncol. 2016;114:971-976. © 2016 Wiley Periodicals, Inc.

The risk of postoperative adverse events in patients with underlying cardiac disease undergoing major hepatectomy remains poorly characterized.The NSQIP database was used to identify patients undergoing hemihepatectomy and trisectionectomy. Patient characteristics and postoperative outcomes were evaluated.From 2005 to 2012, 5227 patients underwent major hepatectomy. Of those, 289 (5.5%) had prior major cardiac disease: 5.6% angina, 3.1% congestive heart failure, 1% myocardial infarction, 54% percutaneous coronary intervention, and 46% cardiac surgery. Thirty-day mortality was higher in patients with cardiac comorbidity (6.9% vs. 3.7%, P = 0.008), including the incidence of postoperative cardiac arrest requiring cardiopulmonary resuscitation (3.8% vs. 1.2%, P = 0.001) and myocardial infarction (1.7% vs. 0.4%, P = 0.011). Multivariate analysis revealed that functional impairment, older age, and malnutrition, but not cardiac comorbidity, were significant predictors of 30-day mortality. However, prior percutaneous coronary intervention was independently associated with postoperative cardiac arrest (OR 2.999, P = 0.008).While cardiac comorbidity is not a predictor of mortality after major hepatectomy, prior percutaneous coronary intervention is independently associated with postoperative cardiac arrest. Careful patient selection and preoperative optimization is fundamental in patients with prior percutaneous coronary intervention being considered for major hepatectomy as restrictive fluid management and low central venous pressure anesthesia may not be tolerated well by all patients.

While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9–4.9) and 23.9 % (95 % CI, 19.6–28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7–23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9

While survival after malignancies is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant by accounting for "accrued" survival time as time progresses. We sought to compare actuarial and CS among patients with gallbladder carcinoma (GBC) .A total of 312 patients who underwent curative intent surgery for GBC between 2000 and 2014 were identified using a multi-institutional database. Overall survival (OS) was estimated using the Kaplan-Meier method. CS was calculated as the probability of surviving an additional 3 years at year "x" after surgery using the formula CSAmong all patients, the median actuarial OS was 24.8 months (IQR 13.3-88.9). While actuarial survival decreased over time, 3-year CS (CSCS provides a more accurate, dynamic estimate for survival, especially among high-risk patients. CS estimates can be used to accurately predict survival and guide clinical decision making.

Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC. Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed. Median survival was 24.4 months; 3- and 5-year survival was 37.2 and 20.8 %, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration. The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated.

Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2-9] vs. no CBD, 3 [IQR: 1-7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87-2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22-7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70-30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26-5.31, P = 0.010) were predictive of a worse OS.CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. 2016;114:176-180. © 2016 Wiley Periodicals, Inc.

Although the American Joint Committee on Cancer (AJCC) classification is the most accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA), other LN prognostic schemes have been proposed. This study sought to define the performance of the AJCC LN staging system relative to the number of metastatic LNs (NMLN), the log odds of metastatic LN (LODDS), and the LN ratio (LNR). Patients who underwent curative-intent resection for GBA between 2000 and 2015 were identified from a multi-institutional database. The prognostic performance of various LN staging systems was compared by Harrell’s C and the Akaike information criterion (AIC). Altogether, 214 patients with a median age of 66.7 years (interquartile range [IQR] 56.5–73.1) were identified. A total of 1334 LNs were retrieved, with a median of 4 (IQR 2–8) LNs per patient. Patients with LN metastasis had an increased risk of death (hazard ratio [HR] 1.87; 95 % confidence interval [CI] 1.24–2.82; P = 0.003) and recurrence (HR 2.28; 95 % CI 1.37–3.80; P = 0.002). In the entire cohort, LNR, analyzed as either a continuous scale (C-index, 0.603; AIC, 803.5) or a discrete scale (C-index, 0.609; AIC, 802.2), provided better prognostic discrimination. Among the patients with four or more LNs examined, LODDS (C-index, 0.621; AIC, 363.8) had the best performance versus LNR (C-index, 0.615; AIC, 368.7), AJCC LN staging system (C-index, 0.601; AIC, 373.4), and NMLN (C-index, 0.613; AIC, 369.5). Both LODDS and LNR performed better than the AJCC LN staging system. Among the patients who had four or more LNs examined, LODDS performed better than LNR. Both LODDS and LNR should be incorporated into the AJCC LN staging system for GBA.

Extrahepatic biliary malignancies are often diagnosed at an advanced stage. We compared patients with unresectable perihilar cholangiocarcinoma (PHCC) and gallbladder cancer (GBC) who underwent a palliative procedure versus an aborted laparotomy. Seven hundred seventy-seven patients who underwent surgery for PHCC or GBC between 2000 and 2014 were identified. Uni- and multivariable analyses were performed to identify factors associated with outcome. Utilization of preoperative imaging increased over time (CT use, 80.1 % pre-2009 vs. 90 % post-2009) (p

Duodenal neuroendocrine tumors (NETs) are rare neoplasms with poorly defined management. We sought to evaluate the outcomes of patients undergoing resection of duodenal NETs.Using a multi-institutional database, 146 patients who underwent resection for duodenal NETs between 1993 and 2015 were identified. Data on clinicopathologic characteristics and outcomes were collected and analyzed.Local surgical resection (LR) was performed in 57 (39.0 %) patients, while 50 (34.3 %) patients underwent pancreaticoduodenectomy (PD) and 39 (26.7 %) patients an endoscopic resection (ER). Factors associated with worse RFS included advanced tumor grade and metastasis at diagnosis (both P 0.05) but not procedure type (P 0.05). Among patients who had at least one lymph node examined (n = 85), 50 (58.8 %) had a metastatic lymph node; lymph node metastasis (P = 0.04) and advanced tumor grade (P = 0.04) were more common among patients with tumors1.5 cm. Median length-of-stay was longer for PD versus LR (P 0.001). PD patients were at increased risk for severe postoperative complications (P = 0.01).Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors ≤1.5 cm, LR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.

Minimally invasive liver surgery is a growing field, and a small number of recent reports have suggested that laparoscopic liver resection (LLR) is feasible even in patients with cirrhosis. However, parenchymal transection of the cirrhotic liver is challenging due to fibrosis and portal hypertension. There is a paucity of data regarding the technical modifications necessary to safely transect the diseased parenchyma. Patients undergoing LLR by a single surgeon between 2008 and 2015 were reviewed. Patients with cirrhosis were compared to those without cirrhosis to examine differences in surgical technique, intraoperative characteristics, and outcomes (including liver-related morbidity and general postoperative complication rates). A total of 167 patients underwent LLR during the study period. Forty-eight (29 %) had cirrhosis, of which 43 (90 %) had hepatitis C. Most had Child–Pugh class A disease (85 %). Compared to noncirrhotics, patients with cirrhosis were older, had more comorbidities, and were more likely to have hepatocellular carcinoma. Precoagulation before parenchymal transection was used more frequently in cirrhotics (65 vs. 15 %, P

Background Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy. Methods Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis. Results In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P 001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P 001) and metastasectomy (36.9 vs 17.3 months, P = .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections ( P = .008). Margin status at metachronous metastasectomy was not associated with survival ( P = . 452). Conclusion Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.

Background. Retroperitoneal sarcomas (RPS) comprise approximately 15% of all soft-tissue sarcomas and frequently associated with significant morbidity and as little as 30% 5-year survival. Here, we provide a large, contemporary, and multi-institutional experience to determine which tumor, patient, and treatment characteristics are associated with long-term outcomes in RPS. Methods. 571 patients with primary RPS were identified from the United States Sarcoma Collaboration (USSC). RPS patients who underwent resection from January 2000 to April 2016 were included with patient, tumor, and treatment-specific variables investigated as independent predictors of survival. Survival analyses for disease-free and overall survival were conducted using Kaplan–Meier and Cox proportional hazards model methods. Results. The study cohort was 55% female, with a median age of 58.9 years (IQR: 48.6–70.0). The most common tumor histiotypes were liposarcoma (34%) and leiomyosarcoma (28%). Median follow-up was 30.6 months (IQR: 11.2–60.4). Median disease-free survival was 35.3 months (95% CI: 27.6–43.0), with multivariate predictors of poorer disease-free survival including higher grade tumors, nodal-positive disease, and multivisceral resection. Median overall survival was 81.6 months (95% CI: 66.3–96.8). Multivariate predictors of shorter overall survival included higher grade tumors, nodal-positive and multifocal disease, systemic chemotherapy, and grossly positive margins (R2) following resection. Conclusions. The strongest predictors of disease-free and overall survival are tumor-specific characteristics, while surgical factors are less impactful. Nonsurgical therapies are not associated with improved outcomes despite persistent interest and utilization. Complete macroscopic resection (R0/R1) remains a persistent potentially modifiable risk factor associated with improved overall survival in patients with retroperitoneal sarcomas.

Management of asymptomatic small well-differentiated (panNET)2 cm remains controversial. A consensus conference was held on this topic. The impact of attending the conference and participating in the audience response survey on surgeon's clinical approach to pancreatic neuroendocrine tumors was assessed.Audience members were surveyed using a smartphone real-time response system at the beginning and end of the conference.The majority of 75 attendees underwent fellowship training, and 30% had10 years experience as attending surgeons. Previously published consensus statements on the topic were considered insufficient to guide surgical practice by 82% of attendees, and over 96% desired additional data. After review of the data, consensus statements, and decision-making process, a significant number of participants changed their opinions regarding indications for tissue biopsy (p = 0.001), size thresholds for excision (p = 0.002), and regional lymph node dissection (p = 0.002) independent of whether a consensus was reached by the content-expert panel.This represented the first Delphi process consensus on the topic, and the survey confirmed the topic as well-chosen and timely. Attendees changed opinions on management of panNET regardless of whether formal consensus was reached. Therefore, statements of consensus combined with presentation of literature and live discussion served to impact attendees' approach to this disease.

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. 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. 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). 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.

BACKGROUND AND OBJECTIVES: Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown. METHODS: All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated. RESULTS: Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to notransfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1–3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1–5.1; P = 0.035). CONCLUSIONS: Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.