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Background Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. Methods Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. Discussion These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. Trial registration Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.

Background: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. Methods: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. Results: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). Conclusion: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM., SCOPUS: ar.j, info:eu-repo/semantics/published

Erica Locatelli,1,* Yan Li,2,* Ilaria Monaco,1 Wei Guo,3 Mirko Maturi,1 Luca Menichetti,4 Paolo Armanetti,4 Robert C Martin,2 Mauro Comes Franchini1 1Department of Industrial Chemistry “Toso Montanari”, Bologna, Italy; 2Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, USA; 3Department of Hematology, The First Hospital of Jilin University, Changchun, China; 4Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy *These authors contributed equally to this work Introduction and purpose: Cancer stem cells (CSCs) present a higher capacity to evade being killed by cancer agents and developing chemoresistance, thus leading to failure of conventional anticancer therapeutics. Nanomaterials specifically designed for targeting and treating not only tumor cells, but also CSCs, may encompass therapeutic and diagnostic tools, thus successfully eradicating the tumor. Materials and methods: Polymeric micelles simultaneously loaded with gold nanorods (GNRs) and Adriamycin were prepared and used as a novel therapeutic and diagnostic weapon. Epithelial cell adhesion molecule (EpCAM) is an important CSC surface marker and has been exploited in this work as an active targeting agent. Photoacoustic imaging was applied for GNR individuation and tissue recognition. Results: The nanosystem was demonstrated to be able to elicit effective targeting of cancer cells and cause their killing, in particular under laser ablation. Moreover, ex vivo photoacoustic imaging is able to clearly identify tumor regions thanks to GNR’s contrast. Conclusion: The nanosystem can be considered a powerful and promising theranostic weapon for hepatocellular carcinoma treatment. Keywords: gold nanorods, drug delivery, photoacoustic imaging, photothermal therapy, EpCAM, cancer stem cells

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.

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

Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well. Data was analyzed from the US Extrahepatic Biliary Consortium database, which retrospectively reviewed patients who received resection of extrahepatic biliary malignancies at 10 high-volume centers. Driving distance to the patient’s treatment center was measured for 1025 patients. These were divided into four quartiles for analysis

Background The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma. Methods Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes. Results The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not. Conclusions The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.

Background. Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. Methods. This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. Results. Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. Conclusion. Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230)

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN.To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma.Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma.Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy.A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years.Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.

Background: The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. Methods: Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers. Results: In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p

Seventh AJCC distal cholangiocarcinoma T-stage classification inadequately separates patients by survival. This retrospective study aimed to define a novel T-stage system to better stratify patients after resection.Curative-intent pancreaticoduodenectomies for distal cholangiocarcinoma (1/2000-5/2015) at 10 US institutions were included. Relationships between tumor characteristics and overall survival (OS) were assessed and incorporated into a novel T-stage classification.176 patients (median follow-up: 24mo) were included. Current AJCC T-stage was not associated with OS (T1: 23mo, T2: 20mo, T3: 25mo, T4: 12mo; p = 0.355). Tumor size ≥3 cm and presence of lymphovascular invasion (LVI) were associated with decreased OS on univariate and multivariable analyses. Patients were stratified into 3 groups [T1: size3 cm and (-)LVI (n = 69; 39.2%); T2: size ≥3 cm and (-)LVI or size3 cm and (+)LVI (n = 82; 46.6%); and T3: size ≥3 cm and (+)LVI (n = 25; 14.2%)]. Each progressive proposed T-stage was associated with decreased median OS (T1: 35mo; T2: 20mo; T3: 8mo; p = 0.002).Current AJCC distal cholangiocarcinoma T-stage does not adequately stratify patients by survival. This proposed T-stage classification, based on tumor size and LVI, better differentiates patient outcomes after resection and could be considered for incorporation into the next AJCC distal cholangiocarcinoma staging system.

While traditional survival analyses focus on factors determined at the time of surgery, conditional survival (CS) estimates prognosis relative to time following treatment. We sought to compare actuarial and CS among patients undergoing curative intent surgery for hilar cholangiocarcinoma.242 patients undergoing surgery between 2000 and 2014 were identified using a multi-institutional database. CS was calculated as the probability of surviving an additional 3 years, given that the patient had already survived "x" years from surgery.Median patient age was 67 years (IQR: 57-73) and most patients were male (n = 140, 57.9%). Lymph node metastases were noted in 79 (32.6%) patients while an R0 margin was obtained in 66.1% (n = 160). Median OS was 22.3 months. Actuarial survival decreased over time from 46.3% at 2 years following surgery to 18.2% at 5 years; in contrast, the 3-year CS (CS3) increased with time (CS3 at 2 years was 39.3% versus 54.4% at 5 years). CS3 exceeded actuarial survival for high-risk patients with patients with perineural invasion demonstrating an actuarial survival of 15.4% at 5 years versus CS3 of 37.6% at 2 years following surgery (Δ = 22.2%).CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients.

Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established.A national cadre of pancreatic surgeons was surveyed regarding perceived quality metrics, which were evaluated against the Central Pancreas Consortium (CPC) database to determine actual performance and relationships with long-term outcomes.The most important metrics were perceived to be participation in clinical trials, appropriate clinical staging, perioperative mortality, and documentation of receipt of adjuvant therapy. Subsequent analysis of 1399 patients in the CPC dataset demonstrated that a R0 retroperitoneal and neck margin was obtained in 79% (n = 1109) and 91.4% (n = 1278) of cases, respectively. 74% of patients (n = 1041) had10 lymph nodes harvested, and LN positivity was 65% (n = 903). 76% (n = 960) of eligible patients (surgery first approach) received adjuvant therapy within 60 days of surgery. Multivariate analysis demonstrated margin status, identification of10 lymph nodes, nodal status, tumor grade and delivery of adjuvant therapy within 60 days to be associated with improved overall survival.These analyses demonstrate that systematic monitoring of surgeons' perceived quality metrics provides critical prognostic information, which is associated with patient survival.

BACKGROUND: The role of routine lymphadenectomy for perihilar cholangiocarcinoma is still controversial and no study has defined the minimum number of lymph nodes examined (TNLE). We sought to assess the prognostic performance of American Joint Committee on Cancer/Union Internationale Contre le Cancer (7th edition) N stage, lymph node ratio, and log odds (LODDS; logarithm of the ratio between metastatic and nonmetastatic nodes) in patients with perihilar cholangiocarcinoma and identify the optimal TNLE to accurately stage patients. METHODS: A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 1995 and 2014. The prognostic abilities of the lymph node staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE. RESULTS: One hundred and fifty-eight (36.2%) patients had lymph node metastasis. Median TNLE was 3 (interquartile range, 1 to 7). The LODDS had a slightly better prognostic performance than lymph node ratio and American Joint Committee on Cancer, in particular among patients with 2, the hazard ratio for N1 patients was statistically significant and the hazard ratio for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. Although the 5-year overall survival of N1 patients was only slightly affected by TNLE, the 5-year overall survival of N0 patients increased significantly with TNLE. CONCLUSIONS: Perihilar cholangiocarcinoma patients undergoing radical resection should ideally have at least 4 lymph nodes harvested to be accurately staged. In addition, although LODDS performed better at determining prognosis among patients with = 4 TNLE. (C) 2016 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Background: Image-guided ablation is used to treat patients with unresectable malignant hepatic tumors that are limited in number and size, especially hepatocellular carcinoma (HCC) and colorectal hepatic metastases. While radiofrequency ablation (RFA) has been the most popular technique, several alternate options for focal tissue destruction have recently attracted attention. These technologies appear to be able to overcome some specific limitations of RFA. Currently, there is no accepted algorithm for the use of the different techniques for image-guided ablation. Summary: A panel of physicians practicing in North America or Europe met to develop a set of recommendations aimed at providing directions for clinical validation of energy-based, thermal and non-thermal image-guided ablation technologies in the treatment of malignant liver tumors. The recommendations were developed through a critical appraisal of potential advantages and disadvantages of each ablation technology, based on experimental findings and available data, as well as on critical considerations for their clinical validation in hepatic tumor treatment from a Western perspective. Key Messages: Significant variability appears to exist among the different equipment and devices within each type of technology. A comprehensive understanding of the data and a critical appraisal of the efficacy and safety profile of each ablation system is required. Clinical practice guidelines should include specific information of the recommended techniques and protocols instead of a generic indication of the technology.

Inflammation and oxidative stress are the key events in carcinogenetic transformation. Black raspberries (BRB) have been demonstrated to have antioxidant, anti-inflammatory and anti-cancer bioactivities. In this study, a concanavalin A induced hepatitis mouse model is used to examine the effect of BRB extract on hepatic injury. Three BRB extracts, including ethanol/H2O extracts (both anthocyanin-contained fraction and non-anthocyanin-contained fraction) and hexane extract were used. The alterations in hepatic histology, apoptosis and oxidative stress were observed in the animals pretreated with BRB extracts and then challenged by concanavalin A. Results indicate that ethanol/H2O extracts can inhibit Con A induced liver injury. The hepatic protection by the ethanol/H2O BRB extracts is associated with decreases of lipid peroxidation and NDA oxidative damage. Importantly, the BRB extracts increase manganese superoxide dismutase (MnSOD) activity but not the CuZnSOD. The preservation of MnSOD by BRB extracts is associated with the protective action in the liver challenged by Con A. Ethanol/H2O BRB extracts function as antioxidants, thus demonstrating the critical role of oxidative stress in the Con A induced liver injury, and providing evidence that the protective effects of ethanol/H2O BRB extracts result, at least in part, from their antioxidant action.

Yan Li,1 Andre M Gobin,2 Gerald W Dryden,3 Xinqin Kang,1 Deyi Xiao,1 Su Ping Li,1 Guandong Zhang,2 Robert CG Martin11Department of Surgery, 2Department of Bioengineering, 3Division of Medicine, University of Louisville School of Medicine, Louisville, KY, USAAbstract: Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer.Keywords: carcinoma, gold nanoparticles, ablation, near infrared, chitosan, drug uptake, cancer

Background Irreversible electroporation (IRE) is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. “Learnability” and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. Methods Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1st 50 patients treated), B (2nd 50) and C (3rd 50 patients treated) chronologically and analyzed for outcomes. Results A total of 167 IRE procedures were performed, with a majority being liver(39.5%) and pancreatic(35.5%) lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9vs3cm,p=0.001), more numerous lesions (3.2vs2.2,p=0.07), more vascular invasion(p=0.001), underwent more associated procedures(p=0.001) and had longer operative times(p

Introduction. There has been limited reporting on the use of hepatic-directed therapy in liver dominant hepatic metastases arising from pancreatic cancer.Methods. An IRB-approved prospective multi-institutional treatment registry of 885 patients undergoing 1458 treatments for primary or secondary cancers in the liver was evaluated from January 2007 to January 2011.Results. Ten patients underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six patients received concurrent chemotherapy while undergoing DEB with no severe adverse events. After a median followup of 16 months, the 6- and 12-month response rates were 80% and 75%, respectively, with a median overall survival of 9.3 months.Conclusion. Hepatic arterial therapy with DEB can be safely and effectively used in selected patients with liver predominant metastatic disease from pancreatic cancer. This therapy should be considered in combination with systemic chemotherapy as a possible second therapy given the limited response rates of second-line chemotherapy.

Curcuma longa is a perennial member of the Zingiberaceae family, and cultivated mainly in India, and Southeast Asia. The hypothesis for this study is that turmeric will have distinctive effects from curcumin due to the presence of other bioactive compounds. Thirty Eight-week old Sprague-Dawley rats were separated into three oral feeding groups. Group 1, standard rat chow, Control diet - AIN 93M, group 2 - Curcumin - 700ppm or 0.7g/kg diet, and group 3 - Turmeric - 14,000ppm or 14g/kg diet for a total of 3weeks. One group of rats were feed all three diets only and another group underwent esophagoduodenal anastomosis to evaluate the effects of bioavailability. Curcumin diet did not increase the transcription of mRNA of TNF-alpha, IL-6, iNOS, and COX-2. The average fold change in the mRNAs level was not significant. Whereas turmeric diet increases the levels of IL-6 (1.9-fold, p=0.05), iNOS (4.39-fold, p=0.02), IL-8 (3.11-fold, p=0.04), and COX-2 (2.02-fold, p=0.05), suggesting that turmeric either was more bioavailable or had more affect on pro-inflammatory genes compare to curcumin diet. We have demonstrated the molecular effects of curcumin and turmeric in the role as an anti-inflammatory therapy. However, significant bioavailable differences do occur and must be considered in further chemopreventative investigative trials the setting of reflux esophagitis, Barrett's esophagus, and other upper gastrointestinal cancers.

Background Bile acids are implicated as etiologic agents in esophageal cancer. We sought to analyze the impact of bile acid exposure on esophageal epithelial cells, Barrett's metaplastic cells (BE), esophageal adenocarcinoma cells (EAC), and esophageal squamous carcinoma cell (ESC). We sought to determine if cellular resistance is related to manganese superoxide dismutase expression. Methods Cells were exposed to sodium choleate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), sodium taurocholate (TCA), or a 1:1 mixture (MIX) of reagents at concentrations in the range 0.2–0.8 mM. Cell viability was evaluated by MTT assay. Manganese superoxide dismutase (MnSOD) expression was analyzed by Western blot. Statistical analysis was performed using SPSS ver. 17.0, SPSS Inc., Chicago, IL. Results Bile salt exposure inhibited cell viability in esophageal squamous cells in time- and growth-dependent manner. There was a 50% decrease in cell viability from 4 to 24 h. BE, EAC, and ESC cell lines were more resistant to bile insult. In untreated cell lines, MnSOD expression was significantly decreased in EAC and ESC cell lines compared with esophageal squamous epithelial cells and BE cells ( P = 0.002). Exposure of ESC cells to bile salt increased MnSOD expression. Conclusion The confirmation of the role of reactive oxygen species (ROS) and bile acids in esophageal carcinogenesis has interesting implications for chemoprevention in patients with reflux esophagitis and Barrett's esophagus. Further studies are necessary to assess the preventative role of antioxidant supplementation.

The purpose of this study was to evaluate the patient tolerance and efficacy of delivering locoregional chemotherapy to metastatic colorectal (MC) hepatic metastases via hepatic trans-arterial approach using irinotecan loaded drug eluting beads. This open-label, multi-center, single arm study included 30 MC patients, who had failed first line therapy. Of the 57 total embolization sessions, 12 (21% of sessions) were associated with adverse reactions during or after the treatment. After a median followup of 9 months, response rates by modified RECIST were 75% at 3 months and 66% at 6 months. Hepatic trans-arterial therapy using Irinotecan loaded DCBeadTMwas safe and effective in the treatment of MCC as demonstrated by a minimal complication rate and acceptable tumor response.

Background. Esophagectomy for esophageal cancer is being practiced routinely with favorable results at many centers. We sought to determine if tumor histology is a powerful surrogate marker for perioperative morbidity.Methods. Seventy three consecutive patients managed operatively were reviewed from our prospectively maintained database.Results. Adenocarcinoma (AC) was present in 52 (71%) and squamous cell (SCC) in 21 (29%). The use of neoadjuvant therapy was similar for the AC (34.62%) and SCC (42.86%) groups. The SCC group had a higher incidence of prior pulmonary disease than the AC group (23.8% versus 5.8%, resp.; SCC patients were more likely to have a prolonged ICU stay than AC patients () despite similar complication rates, EBL, and prognostic nutritional index. The SCC group did, however, experience higher grades of complications ().Conclusions. Presence of SCC was the single best predictor of prolonged ICU stay and more severe complications as defined by this study. Only a past history of pulmonary disease was different between the two histologic subgroups.

Previous studies have suggested a variety of factors that may affect the false negative (FN) rate for sentinel lymph node (SLN) biopsy in breast cancer. Because FN results are relatively rare, no prior studies have had sufficient sample size to allow detailed statistical analysis of factors predicting FN results.Patients with clinical stage T1-2, N0 invasive breast cancer were enrolled in a prospective, multicenter study. All patients underwent SLN biopsy, followed by planned completion axillary dissection regardless of the SLN results, to assess the FN rate. SLN biopsy was performed using radioactive colloid injection in combination with isosulfan blue dye in 94% of cases. Dermal, subdermal, peritumoral, or subareolar radioactive colloid injection techniques were used at the discretion of each institution. Univariate and multivariate analyses were performed to identify factors associated with a FN result.SLNs were identified in 3870 of 4117 patients (94%). There were 1243 true positive, 2521 true negative, and 106 FN results. Age, histologic subtype, the number of non-SLN removed, tumor palpability, type of breast biopsy, and SLN injection technique were not significant factors. On multivariate analysis, tumor size2.5 cm, upper outer quadrant tumor location, removal of only a single SLN, minimal surgeon experience, presence of a single positive axillary LN, and use of immunohistochemistry (IHC) for SLN analysis were independently associated with an increased risk of FN results.Surgeon experience, tumor size and location, and the number of SLN removed are preoperative and intraoperative factors that independently predict the risk of a FN result. In contrast to suggestions from other smaller studies, age does not affect the likelihood of a FN result; a lesser, rather than greater, number of positive axillary nodes was associated with an increased likelihood of a FN result; and IHC analysis of the SLN increases, rather than decreases, the risk of FN results.

To characterize factors predictive of improved survival following gastrectomy with additional organ resection for the treatment of gastric cancer.Recent large series have reported significant survival disadvantages to patients who have undergone gastrectomy with splenectomy or pancreaticosplenectomy, and yet gastrectomy with additional organ resection is needed to accomplish an R0 resection in some cases. Gastrectomy with splenectomy and other organ resections has been associated with advanced T-stage, positive resection margins, and higher postoperative morbidity and mortality rather than an absolute predictor of survival.The authors reviewed the Department of Surgery prospective gastric database at Memorial Sloan-Kettering Cancer Center from July 1985 to July 2000. During this period, of the 2,112 patients with primary gastric cancer, 1,133 underwent an R0 resection. The R0 resection group included 865 patients who underwent gastrectomy alone and 268 patients who underwent gastrectomy with another organ resection. Clinicopathologic, operative, complication, and survival data were compared between these two groups. Chi-square analysis and the Kaplan-Meier method were used to compare and estimate median survival.The most common organs resected were the spleen and pancreas, with an even distribution of other organs. Pathologic factors revealed that the gastrectomy with organ resection group had significantly larger lesions, greater T-stage, and a higher incidence of advanced nodal disease than the group who did not undergo additional organ resection. The incidence of pathologically confirmed T4 cancers in the additional organ resection group was only 14%. The overall 5-year survival rate for patients with T3/T4 disease was 27% with additional organ resection. The overall 5-year survival rate for the gastrectomy with organ resection group (32%, median 32 months) was significantly less than the group that did not undergo additional resection (50%, median 63 months) on univariate analysis. However, additional organ resection was not a predictor of survival on multivariate analysis. Multivariate analysis identified advanced T-stage (T3 or greater) and nodal stage (N1 or greater) as adverse predictors of survival in this group.Long-term survival following gastrectomy with additional organ resection is possible. Depth of invasion and the extent of lymph node metastasis are the most important predictors of survival following gastrectomy with additional organ resection, and a R0 resection has been achieved. Judicious use of additional organ resection for the treatment of advanced gastric cancer must be emphasized, given the increased overall morbidity and infrequent finding of actual T4 disease. Additional organ resection can be performed with minimal morbidity and can improve the chance of overall survival in patients with advanced T-stage disease.

Although an array of short-term postoperative outcomes such as operative time, estimated blood loss, blood transfusion, length of hospital stay, time to return to work, or hospital charges have been reported, death and complication rates remain the most frequently measured and reported endpoints. With their preeminence as surgical outcome measures, they are often the sole data provided as a means of comparing surgical techniques or perioperative management decisions. Complication reports within both hospitals and the medical literature thus deserve consistency and clarity in reporting. There have been more than 11 million articles annotated in the Index Medicus since 1966, and better than 8,000 new publications are added each week. With this explosion of publications in the medical literature, variability in the quality of the reports inevitably occurs. The ability of the physician to discern these differences in quality requires considerable time, expertise, and insight. This places an increasing burden of responsibility on the journal editors and reviewers of submitted articles to make consistent recommendations to potential authors that will ensure that improved reports meeting minimal standards will be published. This is particularly important for those endpoints, such as surgical complications, that are so frequently portrayed as the prime reason for making changes in patient management. This study was designed to critically evaluate the quality of the surgical literature as it relates to the reporting of complications. Selected articles are assessed for compliance with 10 criteria that judge this quality.

Background Despite the increasing frequency of liver resection for multiple types of disease, caudate lobe resection remains a rare surgical event. The goal of this study is to review our experience and evaluate possible predictors of adverse outcomes in patients undergoing caudate lobectomy. Methods We reviewed a 1,900-patient prospective hepato-pancreatico-biliary database from January 2000 to December 2011, identifying 36 hepatectomy patients undergoing caudate lobe resection. Clinicopathologic characteristic and outcome data were compared using chi-square, T-test, ANOVA, Kaplan-Meier, and Cox regression analysis. Primary endpoints were the incidence and severity of complications, and secondary endpoints were blood loss, hospital stay, and transfusion requirements. Patients were also divided in two groups with group A being patients operated on before December 2007 and group B after 2007. We compared the demographics, risk factors, complication rates, and operative details between the two groups. Results Thirty-six patients underwent caudate lobe resection for cholangiocarcinoma (47.2%), metastatic colorectal cancer (36.1%), hepatocellular carcinoma (8.3%), or benign disease (8.3%). Nine patients (29%) had additional liver resection. Median overall survival (OS) was 21 months. Complications occurred in 52.7% (19/36) of patients with a median grade of 2. Tobacco abuse was associated with an increased risk of operative complications (73.3% vs. 38.9%, p = 0.03). Prior history of cardiac disease was associated with a higher complication rate (87% vs. 42%, p = 0.03). Neoadjuvant chemotherapy, biliary procedures, hepatitis, and prior major abdominal surgery were not predictive of complications. Major complication was also predicted by the volume of RBC transfusion (2.7 vs. 4.1 units, p = 0.003). In our subgroup analysis of the patients undergoing surgery before and after 2007, the two groups were well matched based on age, comorbidities, and risk factors. The complication rates and rates of high-grade complications were similar, but blood loss (600 ml vs. 400 ml, p = 0.03), inflow occlusion time (Pringle time 12.6 vs. 6, p = 0.00), and hospital stay (9.5 vs. 7 days, p = 0.01) were significantly lower in group B. Conclusions With appropriate patient selection, caudate lobe resection is an effective component of surgery for hepatic disease. Tobacco use and prior cardiac history increase the risk of complications.

Background Following failure of standard systemic chemotherapy, the role of hepatic transarterial therapy for colorectal hepatic metastasis continues to evolve as the experience with this technique matures. The aim of this study to gain a better understanding of the value of drug eluting bead therapy when administered to patients with unresectable colorectal hepatic metastasis. Methods This was an open-label, multi-center, single arm study, of unresectable colorectal hepatic metastasis patients who had failed standard therapy from 10/2006-10/2008. Patients received repeat embolizations with Irinotecan loaded beads(max 100 mg per embolization) per treating physician's discretion. Results Fifty-five patients underwent 99 treatments using Irinotecan drug eluting beads. The median number of total treatments per patient was 2(range of 1-5). Median length of hospital stay was 23 hours(range 23 hours - 10 days). There were 30(30%) sessions associated with adverse reactions during or after the treatment. The median disease free and overall survival from the time of first treatment was 247 days and 343 days. Six patients(10%) were downstaged from their original disease status. Of these, four were treated with surgery and two with RFA. Neither number of liver lesions, size of liver lesions or extent of liver replacement(25%) were predictors of overall survival. Only the presence of extrahepatic disease(p = 0,001), extent of prior chemotherapy (failed 1st and 2nd line vs > 2 line failure)(p = 0,007) were predictors of overall survival in multivariate analysis. Conclusion Chemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response.

Background Hepatic artery lymph node (HALN) metastasis in pancreatic adenocarcinoma reportedly confers a survival disadvantage. This has led some authors to propose it as an indicator against pancreaticoduodenectomy (PD). Methods Consecutive patients who underwent PD during 2002–2012 were identified from the University of Louisville prospective hepatopancreaticobiliary database. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis. The log-rank test and multivariate Cox proportional hazards regression were used in further analyses. Results A total of 420 patients underwent PD during the period of study, of whom 197 had lymph node (LN) metastasis. Among these, 41 (20.8%) patients had disease-positive HALNs. The HALN was the only site of LN metastasis in only three of the 247 patients (1.2%). Median follow-up was 18.5 months (interquartile range: 4.1–28.2 months). Median OS and DFS were 22.7 months [95% confidence interval (CI) 19.0–26.3] and 12.6 months (95% CI 10.2–15.2). There was no significant difference in median OS between HALN-positive patients (18.4 months, 95% CI 12.3–24.0) and HALN-negative patients (19.7 months, 95% CI 16.7–22.6) ( P = 0.659). On multivariate analysis, the hazard ratio (HR) of death was highest among patients with an LN ratio of >0.2 (HR 1.2, 95% CI 1.1–1.29; P = 0.012) followed by those with poorly differentiated histology (HR 1.09, 95% CI 1.04–1.11; P = 0.029). Conclusions In pancreatic adenocarcinoma patients with LN disease, survival after PD is comparable regardless of HALN status. Therefore, HALN-positive disease should not preclude the performance of PD.

BackgroundThe aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature.MethodsMedline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis.ResultsFifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes.ConclusionQuality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery.