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Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common treatment for peritoneal surface malignancies but no standard carrier solution currently exists for the procedure. This study compared a standard low-dextrose perfusate to a higher-dextrose dialysate that has previously shown favorable impact on perioperative patient outcomes in trauma settings. Materials and methods A single-center retrospective study identified patients undergoing CRS/HIPEC from 2008 to 2019 with recorded dextrose concentration of administered perfusate. An institutional shift to a higher-dextrose solution was made in late 2015. Comparisons of preoperative factors, intraoperative and postoperative glucose levels, and postoperative outcomes were made using the chi-square test, Fisher's exact test, Wilcoxon rank sum test, or repeated measures analysis of variance. Results There were 97 patients in the study, 73 (75%) in the low-dextrose group and 24 (25%) in the high-dextrose group. There was no significant difference in peak intraoperative blood glucose levels between the 1.5% (mean 230 mg/dL) and the 2.5% group (mean 199 mg/dL, P = 0.15). Daily postoperative glucose values were also not statistically different (repeated measures analysis of variance, P = 0.18). Median length of stay was slightly lower for the high-dextrose group (10 d, interquartile range 8-15) than that for the low-dextrose group (12 d, interquartile range 9-17), but was not statistically significant (P = 0.29). Return of bowel function and resumption of diet were similar between the groups. The high-dextrose group had a lower rate of overall complications (20.8%) than the low-dextrose group (49.3%, P = 0.0143). Ninety-day mortality was equivalent between the two groups (2.7% low-dextrose, 4.2% high-dextrose, P = 1.0). Conclusions Use of 2.5% dextrose-containing perfusate appears safe for CRS/HIPEC operations, does not negatively impact intraoperative or postoperative glucose levels, and may be associated with a decreased risk of complications.

Background The preoperative and intraoperative factors that could predict a higher risk of anastomotic/staple line leak for gastric cancer patients has not been accurately defined. Methods Patients who underwent surgery with curative intent for gastric malignancies between 2002 and 2018 were evaluated from a single prospective database. Results A total of 195 patients were evaluated with an overall complication rate of 40%. Anastomotic/staple line leak occurred in 13%, with 4% undergoing reoperation during the same hospitalization. Significant risk factors affecting postoperative complications (POC) were identified in the patients including number of comorbidities (≥2) (HR, 5.30; 95% CI, 1.1–15.3; P = 0.037) and operation type (Total vs Distal) (HR, 2.5; CI 1.08–8.5; p = 0.048). Subset analysis of gastric adenocarcinoma patients demonstrates a five-year overall survival (OS) for patients without perioperative complications was 68%, compared with 41% for patients with POCs (p 0.001). Conclusions In a large single-institutional study, POCs were associated with decreased survival in patients undergoing surgery for gastric adenocarcinoma. Optimizing these patients post-operatively with limited anastomotic stress and enteral feeding tube may allow for a less complicated course.

BACKGROUND Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P

Introduction In women with T1-2 breast cancer and one to two positive axillary lymph nodes (LN) at low risk for recurrence, postmastectomy radiation therapy (PMRT) may provide insufficient benefit to justify its toxicity. This study evaluated the interaction of factors associated with overall survival (OS) after PMRT in these patients. Methods The National Cancer Database was queried for women with T1-2 breast cancer undergoing mastectomy with one to two positive LN identified on lymphadenectomy. Patients were grouped according to number of positive LN and then stratified by PMRT use. Differences in OS were evaluated. Results Multivariable modeling demonstrated an interaction effect of age on the efficacy of PMRT. In patients more than or equal to 60 years old, PMRT was associated with improved survival when adjusting for age and tumor grade in patients with 1 to 2 positive LN (risk ratio = 0.62, 95% confidence interval = 0.40-0.93, P = .018). In patients less than 60 years old, tumor size and grade, but not PMRT, were associated with improved OS. Conclusion For women with T1-2 breast cancer and one to two positive LN, PMRT's association with OS is influenced by age, tumor grade, and number of positive LN. PMRT appears to be associated with improvements in OS in older patients, but not younger patients, regardless of tumor size or nodal status.

Background Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. Methods A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. Results Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. Conclusions MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.

Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE.Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37).In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.

Background Current data on the epidemiology of firearm injury in the United States are incomplete. Common sources include hospital, law enforcement, consumer, and public health databases, but each database has limitations that exclude injury subgroups. By integrating hospital (inpatient and outpatient) and law enforcement databases, we hypothesized that a more accurate depiction of the totality of firearm injury in our region could be achieved. Methods We constructed a collaborative firearm injury database consisting of all patients admitted as inpatients to the regional Level 1 trauma hospital (inpatient registry), patients treated and released from the Emergency Department (ED), and subjects encountering local law enforcement as a result of firearm injury in Jefferson County, Kentucky. Injuries recorded from Jan 1, 2016 to Dec. 31 2020 were analyzed. Outcomes, demographics, and injury detection rates from individual databases were compared to those of the combined collaborative database and compared using chi-square testing across databases. Results The Inpatient Registry (n = 1441) and ED database (n = 1109) were conbined resulting in 2550 incidents in the Hospital database. The law enforcement database consisted of 2665 patient incidents, with 2008 incidents in common with the hospital database and 657 unique incidents. The merged collaborative database consisted of 3207 incidents. In comparison to the collaborative database, the inpatient, total hospital (inpatient and ED) and law enforcement databases failed to include 55, 20, and 17 percent of all injuries respectively. The Hospital captured nearly 94% of survivors but less than 40% of non-survivors. Law enforcement captured 93% of non-survivors but missed 20% of survivors. Mortality (11-26%) and injury incidence were markedly different across the databases. Discussion The utilization of trauma registry or law enforcement databases alone do not accurately reflect the epidemiology of firearm injury and may misrepresent areas in need of greater injury prevention efforts. Level of evidence Level III, retrospective comparative.

Broad patterns of use of the gene signature panel Oncotype DX DCIS and its large-scale impact on postoperative administration of radiation therapy in women with ductal carcinoma in situ of the breast remain unclear. This study sought to evaluate the patterns of use of this gene signature panel in women with ductal carcinoma in situ and the impact of these tools on postoperative radiation therapy administration.The National Cancer Database was queried for women with ductal carcinoma in situ treated with breast-conserving therapy who had information regarding whether a gene signature panel was performed between 2010 and 2015. Demographic characteristics, the characteristics of their ductal carcinoma in situ, and whether they received postoperative radiation therapy were compared among patients who did have a gene signature panel performed and those who did not. Patterns of radiation therapy administration were also evaluated based on the recurrence risk score by the gene signature panel.Gene signature panel use increased over time, with a sharp increase in utilization occurring in 2015 (8.0% in 2015 vs 4.4% in 2014, P.001). Patients with estrogen receptor-positive ductal carcinoma in situ were somewhat more likely to have a gene signature panel ordered (3.9% estrogen receptor positive vs 1.7% estrogen receptor negative, P.001), as were patients with lower-grade ductal carcinoma in situ (4.5% grade I/II vs 3.1% grade III, P.001). Gene signature panel utilization was associated with a decrease in the administration of postoperative radiation therapy (48.6% gene signature panel vs 83.4% no gene signature panel, P.001). Among patients in whom a gene signature panel was performed, postoperative radiation therapy was administered in 81.9%, 72.0%, and 35.9% of patients with high-, intermediate-, and low-recurrence scores, respectively.Gene signature panel use in patients with ductal carcinoma in situ has increased over time and is more commonly used in women with lower-risk, clinicopathologic features to determine the magnitude of benefit afforded by radiation therapy. Gene signature panel use is associated with decreased rates of postoperative radiation therapy administration, particularly among patients with scores suggesting a low rate of recurrence.

The Sunbelt Melanoma Trial, a multicenter, prospective randomized clinical study, evaluated the role of high-dose interferon alfa-2b (HDI) therapy for patients with a single positive sentinel lymph node (SLN) metastasis treated with a completion lymph node dissection (CLND). A second protocol in the trial evaluated the prognostic significance of using molecular markers to identify submicroscopic metastases in sentinel lymph nodes that were negative by routine pathologic analysis. The role of CLND with or without adjuvant HDI was evaluated in this group of patients. The results of the study demonstrated that adjuvant HDI offered no survival benefit for patients with a single positive SLN in terms of disease-free or overall survival. Molecular staging using polymerase chain reaction (PCR) for melanoma markers did not identify a high-risk group of patients at increased risk of melanoma recurrence. Additional treatment of these patients who were PCR-positive with either CLND alone or CLND plus HDI did not improve their survival. Additional studies from the Sunbelt Melanoma Trial helped to validate the operational standards of the SLN biopsy procedure and defined the complication rates for both SLN biopsy and CLND. A prognostic risk calculator has been developed from trial data, and the importance of different micrometastatic tumor burden measurements was reported. Although the Sunbelt Melanoma Trial did not demonstrate an improvement in survival with HDI, it is an important trial that highlights the significance of surgeon-initiated randomized clinical trials that incorporate surgical techniques, molecular biomarkers, and adjuvant therapy.

The risk of sentinel lymph node (SLN) metastasis in melanoma is related directly to tumor thickness and inversely to age. The authors hypothesized that for T2 (thickness 1.1–2.0 mm) melanoma, age, and other factors may be able to identify a cohort of patients with a low risk of SLN metastases. The authors developed logistic regression models to predict positive SLNs in patients undergoing SLN biopsy for T2 melanoma using the National Cancer Database. Classification and regression-tree analysis were used to identify groups of patients with high and low risk for SLN metastases. The prediction model then was applied to a separate data set from a multicenter randomized clinical trial. The study identified 12,918 patients with T2 melanoma undergoing SLN biopsy with clinically node-negative melanoma. In the multivariable analysis, increasing thickness, younger age, lymphovascular invasion (LVI), mitotic rate of 1/mm2 or more, axial location, and Clark level of 4 or 5 were independent risk factors for SLN metastases. A cohort based on age (> 56 years) and no LVI was identified with a relatively low risk (7.8%; 95% confidence interval 7.2–8.4%) of SLN metastases. The independent data set of 1531 patients with T2 melanoma confirmed these findings. Among elderly patients (age > 75 years) with melanoma 1.2 mm or smaller and no LVI, the risk of a positive SLN was 4.9% (95% confidence interval 3.3–7.1%). Younger age and LVI are powerful predictors of SLN metastases for patients with T2 melanoma. This prediction model can inform shared decision-making regarding whether to perform SLN biopsy for older patients with otherwise low-risk T2 melanoma.

A significant proportion of noncommunicable diseases in adults has its roots in adolescence, and this is particularly true for cardiovascular disease and stroke. Detection of vascular and metabolic risk factors at young ages may aid disease prevention.In 2,088 adolescents sampled from the general population of Tyrol, Austria, and South Tyrol, Italy, we systematically assessed the frequency of yet unknown vascular and metabolic risk conditions that require further diagnostic workup or intervention (lifestyle counselling or pharmacotherapy). The health screening included medical history taking, fasting blood analysis, and blood pressure and body measurements and was performed at schools. To recruit a representative sample of adolescents, equal proportions (about 67%) of schools were invited per school type and region.Adolescents were on average 16.4 (standard deviation 1.1) years old, and 56.4% were female. A proportion of 22.8% (95% confidence interval [CI], 19.6-26.3) had previous or current physician-confirmed diseases. The health screening newly detected relevant medical conditions in 45.4% [95% CI, 41.5-49.4] (55.8% [95% CI, 52.7-58.7] in boys and 37.4% [95% CI, 35.0-39.8] in girls, p.001). The most prevalent were elevated blood pressure and hypertension, metabolic syndrome, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and subclinical hypothyroidism. Detection of risk conditions did not depend on socioeconomic status but increased with age and body mass index.Vascular health screening in adolescents at schools has a high diagnostic yield and may aid guideline-recommended prevention in the youth. Implementation should carefully consider national differences in healthcare systems, resources, and existing programs.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe side effect of mostly antiresorptive drugs. The aim of this prospective clinical study was to evaluate the nutritional status in MRONJ patients scheduled for surgical treatment (intraoral soft tissue closure). The following parameters were evaluated: body weight, body height, BMI, nutritional risk index (NRI), bioelectric impedance analysis (BIA), vitamins A, B12, D3, E, K1, folic acid, iron, total protein, transferrin, ferritin, prealbumin, albumin, and zinc. All subjects were admitted to hospital four to five days before surgery and sip-fed with Nutritia Fortimel Compact Protein in addition to regular oral food intake. During surgery, a nasogastric tube was inserted and only removed on hospital discharge five days postoperatively. A total of 58 patients could be included. Half of the MRONJ patients were identified to be at risk for malnutrition. Deficiencies regarding protein levels were revealed, whereas hardly any relevant deficits of micronutrients were noted. The intraoral wound healing four weeks post-surgery was highly satisfactory with a low dehiscence rate of intraoral mucosal sites. Of all parameters analyzed, the dehiscence rate at the last follow-up four weeks post-surgery was significantly influenced by vitamin K, transferrin, and ferritin levels (p = 0.030, p = 0.004, and p = 0.023, respectively). In conclusion, perioperative dietary counselling and appropriate nutritional therapy are important supportive measures in MRONJ patients scheduled for intraoral soft tissue closure.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. Methods Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. Results Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p Conclusions Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination.

Objectives Serological tests detect antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the ongoing coronavirus disease-19 (COVID-19) pandemic. Independent external clinical validation of performance characteristics is of paramount importance. Methods Four fully automated assays, Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total (COV2T) and SARS-CoV-2 IgG (COV2G) were evaluated using 350 pre-pandemic samples and 700 samples from 245 COVID-19 patients (158 hospitalized, 87 outpatients). Results All tests showed very high diagnostic specificity. Sensitivities in samples collected at least 14 days after disease onset were slightly lower than manufacturers’ claims for Roche (93.0%), Abbott (90.8%), and Siemens COV2T (90.3%), and distinctly lower for Siemens COV2G (78.8%). Concordantly negative results were enriched for immunocompromised patients. ROC curve analyses suggest a lowering of the cut-off index for the Siemens COV2G assay. Finally, the combination of two anti-SARS-CoV-2 antibody assays is feasible when considering borderline reactive results. Conclusions Thorough on-site evaluation of commercially available serologic tests for detection of antibodies against SARS-CoV-2 remains imperative for laboratories. The potentially impaired sensitivity of the Siemens COV2G necessitates a switch to the company’s newly filed SARS-CoV-2 IgG assay for follow-up studies. A combination of tests could be considered in clinical practice.

The novel Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a global health concern. Vitamin D (VITD) deficiency has been suggested to alter SARS-CoV-2 susceptibility and the course of disease. Thus, we aimed to investigate associations of VITD status to disease presentation within the CovILD registry. This prospective, multicenter, observational study on long-term sequelae includes patients with COVID-19 after hospitalization or outpatients with persistent symptoms. Eight weeks after PCR confirmed diagnosis, a detailed questionnaire, a clinical examination, and laboratory testing, including VITD status, were evaluated. Furthermore, available laboratory specimens close to hospital admission were used to retrospectively analyze 25-hydroxyvitamin D levels at disease onset. A total of 109 patients were included in the analysis (60% males, 40% females), aged 58 &plusmn, 14 years. Eight weeks after the onset of COVID-19, a high proportion of patients presented with impaired VITD metabolism and elevated parathyroid hormone (PTH) levels. PTH concentrations were increased in patients who needed intensive care unit (ICU) treatment, while VITD levels were not significantly different between disease severity groups. Low VITD levels at disease onset or at eight-week follow-up were not related to persistent symptom burden, lung function impairment, ongoing inflammation, or more severe CT abnormalities. VITD deficiency is frequent among COVID-19 patients but not associated with disease outcomes. However, individuals with severe disease display a disturbed parathyroid-vitamin-D axis within their recovery phase. The proposed significance of VITD supplementation in the clinical management of COVID-19 remains elusive.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective, aggressive approach to treating intraperitoneal carcinomatosis. This study aimed to test the efficacy/safety of an enhanced recovery (ERAS) program after CRS-HIPEC surgery. METHODS: Review of an IRB-approved prospectively maintained HIPEC database from 2003–2019. Adverse events and outcomes related to the primary operation were noted. RESULTS. 125 HIPEC procedures performed met inclusion criteria, with 20 treated through ERAS. There was an improvement in LOS (ERAS: 9, 6.0–28.0; non-ERAS: 11.0, 6.0–45.1, P=0.5), a significant reduction in opioid use during hospitalization (ERAS Total Morphine Equivalents 156 vs Non-ERAS of 856, p

The reality of sexual harassment is unmasking in many fields, and medical trainees constitute a vulnerable and at-risk group. We report the prevalence of sexual harassment among GI, internal medicine, and pediatric residents, with a focus on identifying underlying reasons for lack of victim reporting. A modified previously validated Department of Defense survey on sexual harassment was e-mailed to 261 GI, 132 pediatric, and 271 internal medicine program directors. Three hundred eighty-one residents responded to the survey. Female trainees were more likely to be subject to sexual harassment (83%

Ductal carcinoma in situ (DCIS) is a non-obligate precursor, non-invasive malignancy confined within the basement membrane of the breast ductal system. There is a wide variation in the natural history of DCIS with an estimated incidence of progression to invasive ductal carcinoma being at least 13%-50% over a range of 10 or more years after initial diagnosis. Regardless of the treatment strategy, long-term survival is excellent. The controversy surrounding DCIS relates to preventing under-treatment, while also avoiding unnecessary treatments. In this article, we review the incidence, presentation, management options and surveillance of DCIS. Furthermore, we address several current controversies related to the management of DCIS, including margin status, sentinel node biopsy, hormonal therapy, the role of radiation in breast conservation surgery, and various risk stratification schemes.

Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy. RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients. The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases. A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.

Background The benefit of adjuvant chemotherapy occurs with early initiation, but is commonly delayed due to postoperative complications. Minimally invasive surgery is proven to significantly reduce complications and hospital length of stay. This study compares open versus laparoscopic liver resection in patients requiring adjuvant chemotherapy. Methods 120 consecutive patients with metastatic colorectal liver cancer who underwent liver resection between 2007 through 2012 were reviewed from an IRB prospective database. Results 44 laparoscopic cases were compared to 76 open cases having equivalent resections. Laparoscopic liver resection patients had lower blood loss (276 ml) than patients with open resection (614 ml). Patients with laparoscopy had shorter length of hospital stay (5 days) than patients with open resection (9 days). Patients with laparoscopic resection had a shorter time of chemotherapy initiation postoperatively (24 days v 39 days). Overall complication rates were higher, but statistically insignificant in patients with open resection. Conclusions Our data showed that the shorter LOS with laparoscopic major hepatectomies allows earlier initiation of chemotherapy compared to the open group, without jeopardizing surgical margins or extent of resection. Summary Over the past decade multiple authors have established that, despite occasional longer operating times, laparoscopic liver surgery is associated with reduced blood loss, reduced postoperative morbidity and shorter hospital stay. The purpose of this analysis was to determine if the advantages of a minimally invasive approach correspond to shorter initiation of adjuvant chemotherapy versus an open approach.

Melanoma patients with a single microscopically-positive sentinel lymph node (SLN) are classified as stage III and are often advised to undergo expensive and substantially toxic adjuvant therapy. However, the 5-year survival rate for these patients, with or without adjuvant therapy, varies from 14 to 85 %, representing a heterogeneous biological population with a variable prognosis. We aimed to identify an SLN gene signature to aid in risk stratification of patients with tumor-positive SLNs. Microarray experiments were performed to screen SLN genes in recurrence (N = 39) versus non-recurrence (N = 58) groups in the training dataset. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) assay was applied to confirm the expression of selected SLN genes, which were further verified using an independent validation cohort (N = 30). Area under the receiver operating characteristic curve (AUC) was calculated to evaluate prognostic accuracy of the selected SLN gene panel, and the prognostic value of our SLN gene signature was also compared with the current American Joint Committee on Cancer (AJCC) staging system. We identified two SLN genes (PIGR and TFAP2A) that provided high prognostic accuracy in SLN-positive melanoma patients (AUC = 0.864). These two SLN genes, along with clinicopathological features, can differentiate the high- and low-risk groups in node-positive melanoma patients in this cohort. The two SLN genes, when combined with clinicopathological features, may offer a new tool for personalized patient risk assessment.

Background Sentinel lymph node (SLN) biopsy for melanoma results in accurate nodal staging, which guides treatment decisions. Patients with a negative SLN biopsy in general have a favorable prognosis, but certain subsets are at increased risk for recurrence and death. This study aimed to identify risk factors predictive of prognosis in patients with a tumor-negative SLN biopsy for cutaneous melanoma. Methods In this post-hoc analysis of data from a multicenter prospective randomized trial, clinicopathologic data of patients with cutaneous melanoma ≥1.0 mm Breslow thickness and tumor-negative SLN were analyzed. Disease-free survival, overall survival (OS), and local and in-transit recurrence-free survival were compared by Kaplan-Meier analysis. Risk factors for worse survival were identified with Cox proportional hazard models. Results This analysis included 1,998 patients with tumor-negative SLN with a median follow-up of 70 months. Ulceration, Breslow thickness, nonextremity tumor location, and age ≥45 years were independent risk factors for worse disease-free survival and OS. Breslow thickness and ulceration were the only factors on multivariate analysis that predicted local and in-transit recurrence-free survival. Estimated 5-year OS rates ranged from 55.5 to 95.4% on the basis of the defined risk factors. Conclusion There is a wide range of prognosis among patients with tumor-negative SLN. Breslow thickness, ulceration, age, and anatomic location of the primary melanoma are important independent factors predicting survival and recurrence among such patients. These factors can be used to stratify prognosis among patients with tumor-negative SLN to formulate rational long-term follow-up strategies as well as identify high-risk, SLN-negative patients for clinical trials of adjuvant therapy.

Purpose The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients and Methods Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). Results In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. Conclusion No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI.

In patients with cholangiocarcinoma (CC), management of biliary obstruction commonly involves either up-front percutaneous transhepatic biliary drainage (PTBD) or initial endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. The objective of the study was to compare the efficacy and of initial ERCP with stent placement with efficacy of initial PTBD in management of biliary obstruction in CC. A single-center database of patients with unresectable CC treated between 2006 and 2017 was queried for patients with biliary obstruction who underwent either PTBD or ERCP. Groups were compared with respect to patient, tumor, procedure, and outcome variables. Of 87 patients with unresectable CC and biliary obstruction, 69 (79%) underwent initial ERCP while 18 (21%) underwent initial PTBD. Groups did not differ significantly with respect to age, gender, or tumor location. Initial procedure success did not differ between the groups (94% ERCP vs 89% PTBD, p = 0.339). Total number of procedures did not differ significantly between the two groups (ERCP median = 2 vs. PTC median = 2.5, p = 0.83). 21% of patients required ERCP after PTBD compared to 25% of patients requiring PTBD after ERCP (p = 1.00). Procedure success rate (97% ERCP vs. 93% PTBD, p = 0.27) and rates of cholangitis (22% ERCP vs. 17% PTBD, p = 0.58) were similar between the groups. Number of hospitalizations since initial intervention did not differ significantly between the two groups (ERCP median = 1 vs. PTC median = 3.5, p = 0.052). In patients with CC and biliary obstruction, initial ERCP with stent placement and initial PTBD both represent safe and effective methods of biliary decompression. Initial ERCP and stenting should be considered for relief of biliary obstruction in such patients in centers with advanced endoscopic capabilities.

Background Current data suggests that decreasing VTE incidence may require focus on other factors. This study aimed to identify perioperative risk factors for VTE in patients undergoing surgery for gastrointestinal (GI) malignancy. Methods Patients undergoing surgery for GI malignancy from 2013 to 2016 were grouped according to whether or not they developed a postoperative VTE, and groups were compared along demographic, perioperative, and outcome variables. Results Patients who developed VTE were more likely to be older (67 ± 11 VTE vs. 61 ± 10 no VTE, p = 0.04), male (92% vs. 59%, p = 0.02), and have a history of atrial fibrillation (39% vs. 11%, p = 0.01). They also experienced higher intraoperative blood loss (328 ± 724 mL no VTE vs. 918 ± 1885 mL VTE, p = 0.01). On multivariable analysis, history of atrial fibrillation was independently associated with development of postoperative VTE (odds ratio = 3.83, 95% confidence interval = 1.13–13.05, p = 0.03). Conclusion A prior history of atrial fibrillation independently predicts increased risk of developing VTE after surgery for GI malignancy. Improving understanding of the underlying VTE pathophysiology in these patients can help guide effective prevention strategies.

Background Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC. Methods A single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE). Results Twenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0–305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92–458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem. Conclusion IRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life.

Background Identifying factors associated with nonsentinel lymph node (NSN) metastases in melanoma patients with a single positive sentinel lymph node (SLN) could aid decision making regarding adjuvant therapy. We describe a model for identifying patients with a single positive SLN at low risk for NSN metastasis. Methods Factors associated with NSN metastasis in patients with a primary cutaneous melanoma and a single positive SLN who underwent completion lymph node dissection (CLND) were identified. These factors were used to construct a model for predicting the NSN status. The model was validated using a separate data set from another tertiary referral cancer center. Results In the training data set, 111 patients had a single positive SLN. Of these, 27 had positive NSN. SLN tumor deposit diameter ≥0.75 mm (OR, 3.43; P = 0.047), age ≥40 (OR, 12.14; P = 0.024), and multifocal SLN tumor deposit location (OR, 4.16; P = 0.0096) were independently associated with NSN positivity. Patients with 0 to 1 of these risk factors had a low risk of NSN metastasis in both the training (7.5%) and validation (4.6%) data sets. Conclusions A combination of patient and SLN tumor burden characteristics can help to identify patients with a single positive SLN who are at a low risk of NSN metastasis.

The value of routine primary (intraoperative) drain placement after major hepatectomy remains unclear. We sought to determine if primary drainage led to decreased rates of complications, specifically, intra-abdominal biloma or infection requiring a secondary (postoperative) drainage procedure.All patients who underwent major hepatectomy (≥3 hepatic segments) at 3 institutions, from 2000 to 2012, were identified. Patients with biliary anastomoses were excluded. Primary outcomes were any complication, rate of secondary drainage procedures, bile leak, and 30-day readmission.There were 1,041 patients who underwent major hepatectomy without biliary anastomosis; 564 (54%) had primary drains placed at the surgeon's discretion. Primary drain placement was associated with increased complications (56% vs 44%; p0.001), bile leaks (7.3% vs 4.2%; p = 0.048), and 30-day readmissions (16.4% vs 8.0%; p0.001), but was not associated with a decrease in secondary drainage procedures (8.0% vs 5.9%; p = 0.23). Patients with primary drains demonstrated higher American Society of Anesthesioloigsts (ASA) class, greater blood loss, more transfusions, and larger resections. After accounting for these significant clinicopathologic variables on multivariate analysis, primary drain placement was not associated with increased risk of any complications. Primary drainage was, however, independently associated with increased risk of bile leak (hazard ratio [HR] 2.04; 95% CI1.02 to 4.09; p = 0.044) and 30-day readmission (HR 1.79; 95% CI1.14 to 2.80; p = 0.011). There still was no reduction in the need for secondary drainage procedures (HR 0.98; p = 0.96).Primary intraoperative drain placement after major hepatectomy does not decrease the need for secondary drainage procedures and may be associated with increased bile leaks and 30-day readmissions. Routine drain placement is not warranted.

Background Hospital readmission is becoming a quality measure, despite poor understanding of the risks of readmission. This study examines readmission risk factors after major hepatectomy and develops a predictive model. Study Design A retrospective review was performed on patients who had undergone major hepatectomy at 1 of 3 academic centers between the years 2000 and 2012. Clinicopathologic and perioperative data were analyzed for risk factors of 90-day readmission using logistic regression. A readmission risk score was developed and validated in a separate validation set to determine its predictive value. Results Of 1,184 hepatectomies performed, 17.3% of patients were readmitted within 90 days. Factors associated with readmission include operative blood loss (odds ratio [OR] = 1.00; 95% CI, 1.000–1.001), any postoperative complication (OR = 4.3; 95% CI, 1.8–10.4), a major postoperative complication (OR = 5.7; 95% CI, 3.2–10.2), postoperative pulmonary embolism (OR = 12.2; 95% CI, 1.9–78.4), no postoperative blood transfusion (OR = 3.3; 95% CI, 1.7–6.2), surgical site infection (OR = 5.3; 95% CI, 2.9–10.0), and post-hepatectomy hyperbilirubinemia (OR = 1.1; 95% CI, 1.1–1.2). A scoring system based on these risk factors accurately predicted readmission in the validation cohort. A score of >20 points had a positive predictive value of 30.8% and negative predictive value of 95.6%, and a score >50 had a positive predictive value of 50.9% and negative predictive value of 87.7%. This risk score accurately stratifies readmission risk. Conclusions The risk of hospital readmission within 90 days after major hepatectomy is high and is reliably predicted with a novel scoring system.

Background Tube thoracostomy is a common procedure used in the management of thoracic trauma. Traditional teaching suggests that chest tubes should be directed in specific locations to improve function. Common examples include anterior and superior placement for pneumothorax, inferior and posterior placement for hemothorax, and avoidance of the pulmonary fissure. The purpose of this study was to examine the effect of specific chest tube position on subsequent chest tube function. Methods A retrospective review of all patients undergoing tube thoracostomy for trauma from January 1, 2010, to September 30, 2012, was performed. Only patients undergoing computed tomography scans following chest tube insertion were included so that positioning could be accurately determined. Rib space insertion level and positioning of the tube relative to the lung parenchyma were recorded. The duration of chest tube drainage and the need for secondary interventions were determined and compared for tubes in different rib spaces and locations. For purposes of comparison, tubes placed above the sixth rib space were considered "high," and those at or below it were considered "low." Results A total of 291 patients met criteria for inclusion. Forty-eight patients (16.5%) required secondary intervention. Neither high chest tube placement nor chest tube location relative to lung parenchyma was associated with an increased need for secondary interventions. On multivariate analysis, only chest Abbreviated Injury Scale (AIS) scores, mechanism, and volume of hemothorax were found to be significant risk factors for the need for secondary interventions. Conclusion Chest tube location does not influence the need for secondary interventions as long as the tube resides in the pleural space. The severity of chest injury is the most important factor influencing outcome in patients undergoing tube thoracostomy for trauma. Tube thoracostomy technique should focus on safe insertion within the pleural space and not on achieving a specific tube location. Level of evidence Therapeutic study, level IV.

We introduce a new approach to detect individual microparticles that contain NIR fluorescent dye by multispectral optoacoustic tomography in the context of the hemoglobin-rich environment within murine liver. We encapsulated a near infrared (NIR) fluorescent dye within polystyrene microspheres, then injected them into the ileocolic vein, which drains to the liver. NIR absorption was determined using multispectral optoacoustic tomography. To quantitate the minimum diameter of microspheres, we used both colorimetric and spatial information to segment the regions in which the microspheres appear. Regional diameter was estimated by doubling the maximum regional distance. We found that the minimum microsphere size threshold for detection by multispectral optoacoustic tomography images is 78.9 µm.

Background Renal insufficiency adversely affects outcomes after cardiac and vascular surgery. The effect of preoperative renal insufficiency on outcomes after major hepatectomy is unknown. Study Design All patients who underwent major hepatectomy (≥3 segments) at 3 institutions from 2000 to 2012 were identified. Resections were performed using low central venous pressure anesthesia. Renal function was analyzed by preoperative serum creatinine (sCr) level. Primary outcomes were major complications (Clavien grade III to V), respiratory failure, renal failure requiring hemodialysis, and 90-day mortality. Results One thousand one hundred and seventy patients had preoperative sCr levels available. Renal function was analyzed using sCr dichotomized at 1.8 mg/dL, 1 SD higher than the mean value (0.97 ± 0.79 mg/dL) for the cohort. Twenty-two patients had sCr ≥1.8 mg/dL. Major complications occurred in 279 patients (23.8%), respiratory failure in 62 (5.3%), and renal failure in 31 (2.6%). Ninety-day mortality rate was 5.4%. On multivariate analysis, patients with sCr ≥1.8 mg/dL remained at significantly increased risk for major complications (hazard ratio = 3.94; 95% CI, 1.48–10.49; p = 0.006), respiratory failure (hazard ratio = 4.43; 95% CI, 1.33–14.80; p = 0.014), and renal failure (hazard ratio = 4.75; 95% CI, 1.19–18.97; p = 0.028). Serum Cr ≥1.8 mg/dL was not independently associated with 90-day mortality on multivariate analysis (p = 0.27). Conclusions Preoperative serum creatinine ≥1.8 mg/dL identifies patients at significantly increased risk of postoperative major complications, respiratory failure, and renal failure requiring dialysis. Patients are well selected for major hepatectomy, and few patients with substantial renal insufficiency are deemed operative candidates.

Background The BRAF inhibitor vemurafenib (PLX) has shown promise in treating metastatic melanoma, but most patients develop resistance to treatment after 6 mo. We identified a transmembrane protein, extracellular matrix metalloproteinase inducer (EMMPRIN) as a cell surface receptor highly expressed by PLX-resistant melanoma. Using an S100A9 ligand, we created an EMMPRIN targeted probe and liposome that binds to melanoma cells in vivo, thus designing a novel drug delivery vehicle. Methods PLX-resistant cells were established through continuous treatment with PLX-4032 over the course of 1 y. Both PLX-resistant and sensitive melanoma cell lines were evaluated for the expression of unique cell surface proteins, which identified EMMPRIN as an overexpressed protein in PLX0-resistant cells and S100A9 is a ligand for EMMPRIN. To design a probe for EMMPRIN, S100A9 ligand was conjugated to a CF-750 near-infrared (NIR) dye. EMMPRIN targeted liposomes were created to encapsulate CF-750 NIR dye. Liposomes were characterized by scanning electron microscopy, flow cytometry, and in vivo analysis. A2058PLX and A2058 cells were subcutaneously injected into athymic mice. S100A9 liposomes were intravenously injected and tumor accumulation was evaluated using NIR fluorescent imaging. Results Western blot and flow cytometry demonstrated that PLX sensitive and resistant A2058 and A375 melanoma cells highly express EMMPRIN. S100A9 liposomes were 200 nm diameter and uniformly sized. Flow cytometry demonstrated 100X more intracellular dye uptake by A2058 cells treated with S100A9 liposomes compared with untargeted liposomes. In vivo accumulation of S100A9 liposomes within subcutaneous A2058 and A2058PLX tumors was observed from 6–48 h, with A2058PLX accumulating significantly higher levels (P = 0.001626). Conclusions EMMPRIN-targeted liposomes via an S100A9 ligand are a novel, targeted delivery system which could provide improved EMMPRIN specific drug delivery to a tumor.

Background Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS). Study Design A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥1.0 mm Breslow thickness who underwent SLN biopsy. The following micrometastatic disease burden measurements were recorded: Starz classification, Dewar classification (microanatomic location), maximum diameter of the largest focus of metastasis, maximum tumor area, and sum of all diameters. Univariate and multivariate models and Kaplan-Meier analysis were used to evaluate each classification system. Results We reviewed 204 tumor-positive SLNs from 157 patients. On univariate analysis, all criteria except Starz classification were statistically significant risk factors for NSN metastasis. On multivariate analysis, including Breslow thickness, ulceration, age, sex, and NSN status, maximum diameter (using a cut-off of 3 mm) was the only classification system that was an independent risk factor predicting DFS (hazard ratio 2.31, p = 0.0181) and OS (hazard ratio 3.53, p = 0.0005). By Kaplan-Meier analysis, DFS and OS were significantly different among groups using maximum diameter cut-offs of 1 and 3 mm. Conclusions Maximum tumor diameter outperformed other measurements of metastatic tumor burden, including microanatomic tumor location (Dewar classification), Starz classification, maximum tumor area, and sum of all diameters for prediction of survival. Maximum tumor diameter is a simple method of assessing micrometastatic tumor burden that should be reported routinely.

Gender is an established prognostic factor in cutaneous melanoma; women as a group have a better overall prognosis than men. However, the investigators hypothesized that melanoma in young women may have distinct clinicopathologic features and biologic behavior compared with melanoma in older women, possibly related to tanning bed use and excessive acute episodes of sun exposure.A retrospective analysis was performed of a large multicenter study that accrued patients between 1996 and 2003 and included patients aged 18 to 70 years with cutaneous melanoma ≥1 mm Breslow thickness and no evidence of regional or distant metastatic disease. All women with follow-up data were included. Univariate and multivariate analyses as well as Kaplan-Meier (KM) analysis were performed to test for differences in clinicopathologic variables, disease-free survival (DFS), and overall survival (OS) between female patients ≤40 and40 years of age.A total of 1,056 female patients were divided into 2 groups: those40 years of age (n = 757 [71.7%]) and those ≤40 years of age (n = 299 [28.3%]). Overall, there were no differences in Breslow thickness, ulceration, or sentinel lymph node status between groups. Compared with older women, younger women were more likely to have truncal melanomas (39.5% vs 29.5%, P = .0017) and less likely to have regression of the primary tumor (6.4% vs 11.5%, P = .0208). The mean number of sentinel lymph nodes removed was 2.82 for younger women and 2.29 for older women (P.0001). Multivariate analysis revealed that Breslow thickness, ulceration, and tumor-positive sentinel lymph node were associated with worse DFS in both the younger and older groups; truncal location was associated with worse DFS in the younger group only. The same factors were predictive of OS in both groups, except that ulceration was not significant in the younger patient group. In the younger patient group, the 5-year KM DFS rates were 78.1% for truncal melanomas and 92.5% for nontruncal melanoma locations (P = .0009); the corresponding 5-year KM OS rates were 76.6% and 93.9% (P = .0003). In the older patient group, the 5-year KM DFS rates were 84.1% for truncal and 82.8% for nontruncal melanomas (P = NS), and the corresponding 5-year KM OS rates were 81.6% and 87.5% (P = .0049).Although women with cutaneous melanoma tend to have a better prognosis than men, women ≤40 years of age with primary melanoma of the trunk may represent a subgroup at higher risk for disease recurrence and metastasis.

Background The purpose of this study was to evaluate and compare the incidence of wound complications after laparoscopic component separation (LCS) vs open component separation (OCS) in patients with complex abdominal wall hernias. Methods A retrospective review was performed of all patients who underwent LCS or OCS for repair of a complex abdominal wall hernia at a single institution between 2009 and 2011. Charts were reviewed to identify postoperative wound complications. A computed tomographic scan or physical examination was used for the determination of hernia recurrence. Categoric variables were compared using the Fisher exact test. Univariate and multivariate analyses were performed using linear and Cox regression. Recurrence rates were compared using log-rank tests (Kaplan-Meier method). Results A total of 44 patients underwent LCS (n = 18) or OCS (n = 26). There was no statistically significant difference between categoric variables. Multivariate analysis using wound complications as the dependent variable showed a statistically significantly lower rate of wound complications in the LCS group. Conclusions LCS is associated with a lower rate of wound complications when compared with OCS but yields comparable recurrence rates.

We evaluated the differential expression of several microRNAs (miRNAs) among malignant cells in ascites and matched omental metastasis in patients with epithelial ovarian cancer (EOC). Ascites and omental tumors were collected prospectively from five patients who were undergoing primary surgical cytoreduction. Patient samples were processed and treated with carboplatin, paclitaxel and combination chemotherapy. Cell viability was evaluated and miRNA profiling was performed on both tumor cells from ascites fluid and omental cake. Quantitative real-time PCR (RT-q-PCR) and western blots were used to evaluate expressions of miRNA-21 and miRNA -214 and associated proteins. Malignant cells in ascites showed greater cell viability when treated with carboplatin compared to omental metastasis. A significant up-regulation of miRNA-21 and miRNA-214 was observed in malignant cells of ascites compared to omental metastasis; this was confirmed by both cell viability assay and RT-q-PCR. Ours is the first report that demonstrates significant up-regulation of miRNA-21 and miRNA-214 in tumor cells from ascites of patients with EOC compared to omental metastasis. This finding has important implications for intrinsic carboplatin resistance in these patients.

PURPOSE. Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence. METHODS. We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naїve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers. RESULTS. Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p = 0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p = 0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p = 0.001) by in vitro assay and recurrence at 1 year (p = 0.0125). CONCLUSIONS. LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

Background The importance of the lymph node ratio (LNR) after regional lymphadenectomy for cutaneous melanoma is unknown. Materials and methods A post hoc analysis was performed for patients after the completion of lymphadenectomy for cutaneous melanoma. LNR was calculated as the number of tumor-positive nodes divided by the total number of lymph nodes. Comparison of disease-free survival (DFS) and overall survival (OS) and univariate and multivariate analyses with regard to LNR was performed. Comparison of the performance of LNR to other measurements of lymph node disease was performed. Results A LNR of 0.10 was a significant cutoff point for determining DFS and OS. On multivariate analysis, LNR >0.10 was an independent predictor of DFS and OS without other measures of lymph node disease burden. Patients with LNR >0.10 had worse DFS and OS. Absolute counts of tumor-positive lymph nodes differentiated survival differences better than LNR. LNR was not a significant predictor of survival in patients with neck or axillary dissections but was for inguinal dissections. In multivariate analysis of alternative nodal measures, LNR was an inferior prognostic factor. Conclusions A LNR >0.10 has a negative prognostic significance when it is the only measurement of lymph node disease considered but is an inferior prognostic factor to alternative measures of lymph node disease.

Introduction Accessory spleens located within the pancreatic parenchyma (intrapancreatic accessory spleen, IPAS) pose a unique clinical challenge. In many cases, despite imaging and other diagnostic studies, malignancy cannot be excluded and patients are subjected to pancreatic resection. We review our experience with the presentation, diagnosis, and treatment of patients with IPAS to provide insight into improving pre-operative evaluation of these patients Methods A retrospective chart review identified seven patients who underwent surgical resection of an intrapancreatic spleen at University of Louisville Hospital between 2004 and 2015. Charts were analyzed for presenting symptoms, pre-operative imaging, operative therapy, and final pathologic evaluation. Patients were included in the study if they underwent pancreatic resection for a pancreatic mass and were diagnosed with an IPAS on final pathologic evaluation. Results Patient age ranged from 38 to 72 with a median age of 62.5, including five males and two females. Lesions ranged from 1.4 to 7.4 cm in maximal diameter (mean 3.8 cm). All lesions were identified as round, hypervascular, well-circumscribed masses in the pancreatic tail. The most common pre-operative diagnosis was a non-functioning pancreatic neuroendocrine tumor (NF-PNET). The most common operative approach was laparoscopic distal pancreatectomy and splenectomy. Conclusion IPAS are benign tumors commonly mistaken for pancreatic neoplasms such as NF-PNET. A combination of CT, MRI and nuclear medicine examinations can confirm the diagnosis of IPAS and prevent unnecessary surgical resection.

The relationship between RAS mutation status and outcome for patients undergoing repeat hepatectomy (RH) for recurrent colorectal liver metastases (CLM) has not been defined.The objective of this study was to evaluate the relationship between RAS mutation status and outcome in patients undergoing RH for CLM.All patients who underwent RH for CLM with known RAS mutation status between January 2005 and November 2014 were identified, and the outcomes of patients with and without RAS mutations were compared.Ninety-eight patients underwent RH, of whom 34 (35 %) harbored a RAS mutation. Wild-type (WT) and mutant RAS groups had similar clinicopathologic characteristics. Median recurrence-free survival (RFS) for patients with WT and mutant RAS was 12.2 and 6.1 months, respectively (p = 0.03). Median overall survival (OS) for the WT and mutant RAS patients were 42.5 and 26.6 months, respectively (p 0.01). On multivariate analysis, RAS mutations [hazard ratio (HR) = 1.69, p = 0.04] were associated with worse RFS, while multiple tumors (HR = 1.92, p = 0.045) and RAS mutations (HR = 2.11, p = 0.02) predicted worse OS.Patients with recurrent CLM that harbor RAS mutations have worse RFS and OS than patients with WT RAS, and RAS mutations are independently associated with worse RFS and OS. RAS mutation status should be determined prior to RH, as it may impact treatment decisions.

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma.

Background This study was performed to identify clinicopathologic factors associated with survival in acral lentiginous melanoma. Methods A post hoc analysis of a prospective clinical trial and local database was performed in all patients with acral lentiginous melanomas. Multivariate analyses of factors associated with a tumor-positive sentinel lymph node (SLN) biopsy, disease-free survival (DFS), overall survival (OS), and local and in-transit recurrence-free survival (LITRFS) were performed. Kaplan–Meier survival analyses were performed. Results Eighty-five patients were identified. Age younger than 59 years and Breslow thickness (BT) of 2.0 mm or greater were independent risk factors for a positive SLN. SLN status was the only independent risk factor for DFS and LITRFS on multivariate analysis. A BT of 2.0 mm or greater was the only independent risk factor for OS. SLN status distinguished differences in DFS, OS, and LITRFS on Kaplan–Meier analysis. Conclusions SLN status is the dominant factor for recurrence and survival in acral lentiginous melanoma. BT and ulceration are less important in this histologic subtype.

Background We found that a computer model developed by the American Joint Committee on Cancer (AJCC) melanoma staging committee had limitations for predicting prognosis of patients staged by sentinel lymph node (SLN) biopsy. We sought to develop a model that more accurately predicts prognosis in this population. Study Design Using a data set obtained from a prospective multi-institutional study of 2,507 patients with clinically node-negative melanomas ≥1.0 mm Breslow thickness, we developed a prognostic model using a Cox regression formula incorporating a number of significant clinicopathologic factors. The AJCC model and our model were used to predict 5-year survival from this test data set. The concordance correlation coefficient (CCC) was determined and chi-square tests were performed. Our new prognostic model was validated using an independent data set of 1,001 patients. Results Using the test data set, the CCC for the AJCC model was 0.875; chi-square tests demonstrated statistically significant differences between observed and predicted survivals for numerous clinicopathologic factors. The CCC for our model was 0.976 and none of the chi-square tests was statistically significant. Our model performed similarly well in SLN-negative patients (CCC 0.929) and SLN-positive patients (CCC 0.889). The AJCC model performed well in SLN-negative patients (CCC 0.854), but not in SLN-positive patients (CCC 0.626). Using the validation data set, similar findings were obtained. Conclusions Our prognostic model provides superior survival estimates compared with the AJCC model for patients undergoing SLN biopsy. This online tool is available at www.melanomacalculator.com, and will provide important information that can be used to guide adjuvant therapy decisions and stratification in clinical trials.

A growing body of evidence supports the use of multigene signature panels (MSPs) in predicting recurrence risk in patients with invasive breast cancer. This study aimed to evaluate trends in MSP use over time and the effect of MSPs on administration of postoperative chemotherapy.The National Cancer Database was queried for all women with invasive breast cancer who underwent resection between 2011 and 2014 and had information about performance of an MSP, hormone receptor status, and receipt of chemotherapy. Multigene signature panel use over time was evaluated, and patterns of use of Oncotype DX (ODX) and MammaPrint (MP) were compared.In a total of 476,128 patients, an MSP was obtained in 153,782 (30.2%). Multigene signature panel use increased over time and was associated with a decreased rate of chemotherapy administration (24.6% MSP vs 37.2% no MSP; p0.001). Oncotype DX remained the most common MSP used throughout the study period. Oncotype DX was used more commonly in stage I disease than MP, and MP was used more commonly in stage II and III disease. MammaPrint was more commonly used in hormone receptor-negative patients, human epidermal growth factor receptor 2-positive patients, and patients with positive lymph nodes. Postoperative chemotherapy was administered to a higher proportion of patients assessed with MP than with ODX (41.3% vs 23.4%, respectively; p0.001).Use of MSPs among patients with breast cancer has increased over time and is associated with a decreased use of adjuvant chemotherapy. Oncotype DX continues to be the most widely used MSP, although MP use has increased over time. Future studies are warranted to determine the optimal use of these MSPs in risk assessment and postoperative decision making.

Background Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND). Study Design In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison. Results A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044). Conclusions Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.

Background Adherence to guidelines for the treatment of hospitalized elderly patients with community-acquired pneumonia (CAP) has been associated with improved clinical outcomes. This study evaluated the cost-effectiveness of adherence to guidelines for the treatment of CAP in an elderly hospitalized patient cohort. Methods Data from an international, multicenter observational study for patients age 65 years or older hospitalized with CAP from 2001 to 2007 were used to estimate transition probabilities for a multi-state Markov model traversing multiple health states during hospitalization for CAP. Empiric antibiotic therapy was classified as adherent, over-treated, and under-treated according to 2007 Infectious Disease Society of America/American Thoracic Society IDSA/ATS guidelines. Utilities were estimated from an expert panel of active clinicians. Costs were estimated from a tertiary referral hospital and adjusted for inflation to 2013 US dollars. Costs, utilities, and transition probabilities were all modeled using probability distributions to handle their inherit uncertainty. Cost-effectiveness analysis was based on the first 14 days of hospitalization. Patients admitted to the intensive care unit (ICU) were analyzed separately from those admitted to the ward. Sensitivity analyses with regards to time frame (out to 30 days hospitalization), cost estimates, and willingness to pay values were performed. Results The model parameters were estimated using data from 1635 patients (1438 admitted to the ward and 197 admitted to the ICU). For the ward model, adherence to antibiotic guidelines was the dominant strategy and associated with lower costs (−$1379 and −$799) and improved quality of life compared to over- and under-treatment. In the ICU model, however, adherence to guidelines was associated with greater costs (+$13,854 and + $3461 vs. over- and under-treatment, respectively) and lower quality of life. Acceptance rates across the willingness to pay ranges evaluated were 42–48 % for guideline adherence on the ward and 61–64 % for over-treatment on the ICU. Results were robust over sensitivity analyses concerning cost and utility estimates. Conclusions While adherence to antibiotic guidelines was the most cost-effective strategy for elderly patients hospitalized with CAP and admitted to the ward, in the ICU over-treatment of patients relative to the guidelines was the most cost-effective strategy. Electronic supplementary material The online version of this article (doi:10.1186/s12911-016-0270-y) contains supplementary material, which is available to authorized users.

Objective Presentation of a large series of patients with metastatic melanoma involving the eye and orbit. Design Retrospective clinical study. Participants Thirteen cases of metastatic melanoma involving intraocular tissues, 6 cases of metastatic melanoma in the orbit, and 1 case of metastatic melanoma involving both the eye and the orbit, treated in Lausanne between 1986 and 2002, were identified from the computer files of the ocular oncology and orbitopalpebral surgery units of Jules Gonin Hospital. Methods The analysis is based on the demographic data concerning these patients, clinical data concerning the tumor, the treatment applied, the outcome, and the follow-up. Main outcome measures Clinical presentation of intraocular and orbital metastasis, interval between primary tumor and ocular metastasis, survival of the patients, evaluation of various therapeutic protocols. Results Intraocular metastases (14 cases, 15 eyes) were situated in the choroid in 11 cases (isolated lesion, 6 cases; multiple lesions, 3 cases; diffuse involvement, 2 cases), in the iris and ciliary body in 2 cases, and in the retina and vitreous in 2 other cases. The primary tumor was a cutaneous melanoma in 8 cases, a melanoma of the contralateral eye in 3 cases, a mucosal melanoma in 1 case, and was unknown in 2 cases. The mean interval between the diagnosis of ocular metastases and the patient's death was 8.8 months (range, 1–48 months). The primary tumor in the 7 cases of orbital metastases was a cutaneous melanoma in 5 cases, a uveal melanoma in the contralateral eye in 1 case, and was unknown in 1 case. The mean interval between the diagnosis of orbital metastases and death was 19.7 months (range, 5–48 months). The patients were treated by various protocols. The best results, in terms of both local tumor control and preservation of visual function, were obtained with circumscribed proton beam radiotherapy or external beam irradiation, depending on the site and extent of the tumor. Conclusions Metastatic melanomas to the eye and orbit are rare and generally occur in patients with disseminated metastases during the terminal stages of the disease, with a short life expectancy. Treatment is palliative and, among the various possible treatment options, circumscribed proton beam radiotherapy or global photon beam radiotherapy, at relatively high irradiation doses, seems to achieve the most favorable results.

We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined.To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma.Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015.Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%).Clinical variables associated with a major pathologic response (pathologic complete response or5% residual cancer cells) were evaluated using logistic regression.Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009).Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.

Platinum(IV) complexes are promising candidates as prodrugs for oral application in anticancer chemotherapy. However, only a few Pt(IV) compounds entered (pre)clinical trials, e.g. satraplatin, while most of the others were only tested in vitro. Aim of the study was investigation of the in vivo pharmacological behavior as well as the anticancer activity of two novel platinum(IV) complexes vs. satraplatin. The drugs were selected due to significantly different in vitro cytotoxicity while sharing some physicochemical properties (e.g. lipophilicity). Initial experiments indicated that the highly in vitro cytotoxic compound 1 ((OC-6-33)-dichloridobis((4-ethoxy)-4-oxobutanoato)-bis(ethylamine)platinum(IV)) was also characterized by high drug absorption and tissue platinum levels after oral application. Interestingly, analysis of serum samples using SEC-ICP-MS revealed that the administered drugs have completely been metabolized and/or bound to proteins in serum within 2 h after treatment. With regard to the activity in vivo, the outcomes were rather unexpected: although potent anticancer effect of 1 was observed in cell culture, the effects in vivo were rather minor. Nevertheless, 1 was superior to 2 ((OC-6-33)-diammine(cyclobutane-1,1-dicarboxylato)-bis((4-cyclopentylamino)-4-oxobutanoato)platinum(IV)) after i.p. administration, which was, at least to some extent, in accordance to the cell culture experiments. After oral gavage, both compounds exhibited comparable activity. This is remarkable considering the distinctly lower activity of 2 in cell culture as well as the low platinum levels detected both in serum and tissues after oral application. Consequently, our data indicate that the prediction of in vivo anticancer activity by cell culture experiments is not trivial, especially for orally applied drugs.