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PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1–16.2) for the futile resection cohort versus 45.6 (95% CI 39.1–52.1) for non-futile hepatectomies (p

The purpose of this study was to present the optimal patient selection for esophageal stenting after esophageal resection to investigate possible factors leading to treatment success or treatment failure in these patients. This was a prospective, observational study of patients from January 2005 to May 2019 with an esophageal anastomotic leak that were treated with a self-expandable stent (SES). A total of 34 patients were treated. All achieved technical success (100%); 33 (97%) achieved clinical success. No patient had to have reoperative surgery based on their leak management. The stenting in-hospital mortality was 0% with 1 patient (2%) with a 90-day mortality from possible leak-related death. Patients had their stents removed with a median of 106 days. Stenting for an anastomotic leak after resection offers a safe and effective method of treatment and is successful in the majority of cases. Critical to success is optimal patient selection, adequate leak drainage, and optimal stent selection and placement.

Exocrine pancreatic insufficiency (EPI) occurs when pancreatic enzyme activity in the intestinal lumen is insufficient for normal digestion to occur. The true incidence and diagnosis of EPI after pancreatectomy has not been fully understood and optimized. The aim of this study was to present incidence and diagnostic criteria for EPI after pancreatectomy for cancer and provide a guide for management and optimal therapy in pancreatectomy patients with cancer. A comprehensive review of the literature with publication dates from 2014 to 2019 was performed. A comprehensive diagnostic and treatment algorithm was then created based on literature review and current treatment options. In total, 30 studies were included, 19 combined both pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), 9 for central pancreatectomy, and 2 others. EPI was defined subjectively without definitive testing using any of the established diagnostic studies in the majority of studies 23 (76%). Preoperative EPI was calculated to be 11.52%. Most studies assessed exocrine function at least 6 months postoperatively with four studies extending the follow-up period beyond 12 months. EPI diagnosed postoperatively at 1 month (40.27%), 3 months (30.94%), 6 months (36.06%), and 12 months (34.69%). After PD, the median prevalence of postoperative EPI was 43.14%, CP, the median prevalence was 4.85%, DP, median prevalence of postoperative EPI of 11.94%. EPI is a frequent outcome that is often misdiagnosed or under-reported by the patient post-pancreatectomy. Given the increasing overall survival in pancreatectomy patients for cancer, surgeon awareness and assessment is critical to improving patients’ overall quality of life.

Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy worldwide, is the second leading cause of cancer-related death. Underlying liver dysfunction and advanced stage of disease require treatments to be optimally timed and implemented to minimize hepatic parenchymal damage while maximizing disease response and quality of life. Locoregional therapies (LRTs) such as trans-arterial chemo- and radio-embolization remain effective for intermediate liver-only and advanced HCC disease (i.e., Barcelona-Clinic liver cancer stages B and C) not amendable to primary resection or ablation. Additionally, these minimally invasive interventions have been shown to augment the immune system. This and the recent success of immune-oncologic treatments for HCC have generated interest in applying these therapies in combination with such locoregional interventions to improve patient outcomes and response rates. This report reviews the use of trans-arterial LRTs with immunotherapy for stages B and C HCC, potential biomarkers, and imaging methods for assessing the response and safety of such combinations.

National guidelines suggest routine intraoperative esophagogastroduodenoscopy (EGD) during laparoscopic Heller myotomy (LHM) to assess for mucosal perforation and myotomy adequacy, but the utility of this is unknown. This study aimed to evaluate the effect of intraoperative EGD on outcomes after LHM. Patients who underwent LHM in a single center were retrospectively identified. Outcomes were compared between patients who did and did not undergo intraoperative EGD. Sixty-one patients were reviewed: 46 (75%) underwent intraoperative EGD and 15 (25%) did not. Mucosal perforations occurred in 2 (4%) of the EGD group and 3 (20%) of the non-EGD group (p = 0.06). All perforations, regardless of EGD use, were recognized laparoscopically. There were no postoperative leaks. Failed myotomy occurred in 5 (11%) who underwent EGD and 1 (7%) who did not (p = 0.64). Because EGD does not appear to improve outcomes after LHM, we emphasize its selective, rather than routine, use.

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 Surgical site infections (SSIs) lead to increased morbidity and cost. Negative-pressure wound therapy (NPWT) removes wound exudate and improves local blood flow, but its effect on SSI is unproven following hepatectomy and pancreatectomy. The aim of this trial was to evaluate the effect of NPWT on SSI in this population. Methods Patients were randomized to incisional NPWT or sterile island dressing following surgery. SSI predictive factors were recorded as well as patient comorbidities. Wound complications and type of SSI were recorded prospectively. Results Forty patients received the standardized perioperative bundle. Twenty patients received sterile island: 11 hepatic and 9 pancreatic resections; 20 patients received NPWT: 11 hepatic and 9 pancreatic resections; 23 patients were male; mean age 60.8 years (SD ±10.3); mean BMI 31.7 (SD ±7.0). There were three incisional wound infections: two with sterile island, one with NPWT; six organ space infections: four sterile island and two NPWT. There were no significant differences in SSI rates between groups (P = .57). Conclusion NPWT does not improve SSI rates over simple sterile dressing following hepatectomy or pancreatectomy. Improvements in SSI must be directed toward organ-space infections, which are unaffected by NPWT.

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.

Adequate perioperative nutrition is critical for the success of surgical outcomes. Jejunostomy feeding tube placement may ensure enteral feeding access; however, these types of tubes have had variable reported rates of dysfunction/morbidity. The aim of our study was to report our experience with jejunostomy feeding tube placement and the long-term outcomes following complex foregut surgery. We performed a review of all of our jejunostomy feeding tube placement patients from 1/1/2010 until 7/1/2018. The indication for surgery and primary operation were recorded. All adverse events related to the jejunostomy were recorded during the entire duration of tube access. Social “hassle-factor” issues were also reported, including the number of “jejunostomy-related” phone calls, reinsertion and related placement studies, and readmissions pertaining to jejunostomy-associated complications. During the study period, 542 primary procedures were performed with secondary jejunostomy placement. Jejunostomy-related adverse events occurred in 22.0% of patients (n = 119/542); 12.0% (n = 65/542) were dislodged tubes, 6.0% (n = 30/542) clogged tubes; 5% (n = 25/542) leaking tubes, and 2.8% (n = 15/542) site infections. Tube dysfunctions initiated 244 reinsertion/placement studies in 107 patients, 20 jejunostomy tube-related readmissions, and 78 phone calls to providers for tube dysfunction. Adverse event rates differed significantly between groups (p

OBJECTIVE: To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy. BACKGROUND: Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown. METHODS: Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19–9 decrease ≥50% vs

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

Background Outcomes after laparoscopic gastropexy (LG), performed as an alternative to formal paraesophageal hernia (PEH) repair in patients with giant PEH, have been rarely studied. This manuscript evaluates complications and long-term quality-of-life after LG. Methods An IRB-approved protocol was used to identify patients who underwent LG to alleviate symptoms of acute or chronic gastric obstruction secondary to a paraesophageal hernia. Postoperative outcomes and quality-of-life data were retrospectively collected via chart review and prospectively via phone interview. Results Twenty-six patients underwent LG, with a median age of 76 (52 - 91). Median follow-up was 28 (3 to 55) months. Gastropexy was the chosen intervention due to comorbid conditions (23, 88%), gastric inflammation (2, 8%), or intraoperative instability (1, 4%). Nine (35%) suffered postoperative complications, and 2 (8%) required reoperation. At the time of follow-up, 7 (27%) had died, 3 (11%) could not be reached. Sixteen (62%) completed the follow-up survey. Fourteen (88%) reported symptom resolution. Ten (62%) still required antireflux medication. Median Gastroesophageal Reflux Disease-Health Related Quality of Life score was 4.5 (0 to 19). Fourteen (88%) denied current dietary restrictions. All reported satisfaction with the operation. Conclusion Laparoscopic PEH repair remains the standard of care for the management of giant PEH. However, a subcategory of patients with high operative risk could be candidates for a shorter operative intervention. As our data infers, LG is a reasonable alternative in this patient population. While the continued use of antisecretory medications is sometimes required, LG restores the ability to tolerate full meals without restrictions and results in excellent patient satisfaction.

Background Anti-PDL-1 immunotherapy for Hepatocellular Carcinoma (HCC) demonstrated a mixed response. Polycomb Repressor Complex 2(PRC2) contributes to the initiation and progression of HCC by suppressing tumor antigens and inhibiting an immune response. Two components of epigenetic modulation are Enhancer of Zeste Homolog 2 (EZH2, the catalytic component of PRC2) and DNA Methyltransferase 1 (DNMT1). We aim to investigate the potential role of epigenetic therapy targeting EZH2 and DNMT1 as a novel strategy to modulate immunotherapy response in HCC. Methods HepG2, Hep3B, and Hepa1-6 HCC cell lines were treated with EZH2 inhibitor (DZNep) and DNMT1 inhibitor (5-Azacytidine) with and without anti-PDL-1. Quantitative RT-PCR and immunohistochemistry were performed to evaluate the expression of tumor suppressors, tumor antigens, and Th1 chemokines. In-vivo C57/LJ immunocompetent mice model with subcutaneous tumor inoculation was performed with intraperitoneal drug injections. Results There was a significant upregulation of Th1 chemokines in HepG2 (CXCL9 5.5 ± 0.2 relative fold change; CXCL10 1.44 × 103 ± 37 relative fold change) and Hep3B (CXCL 9 6.85 × 103 ± 1.3 × 103 relative fold change; CXCL 10 2.15 × 103 ± 3.1 × 102 relative fold change). Additionally, there was a significant induction of cancer testis antigens NY-ESO-1 (3.6–3.7 ± 0.3 relative fold change) and LAGE (8.3–11.7 ± 1.9 relative fold change). In vivo model demonstrated statistically significant tumor regression in the combination treatment group (0.02 g ± 0.02) compared to epigenetic therapy (0.63 g ± 0.61) or immunotherapy alone (0.15 g ± 0.21) with untreated control (2.4 g ± 0.71). There was significantly increased trafficking of cytotoxic T- lymphocytes and associated apoptosis for the combination treatment group compared to epigenetic or immunotherapy alone. Conclusions This study demonstrates that epigenetic modulation could be a novel potential strategy to augment immunotherapy for HCC by stimulating T cell trafficking into tumor microenvironment via activation of transcriptionally repressed chemokine genes responsible for T-cell trafficking, inducing previously silent neoantigens for immune targets, and allowing tumor regression as a result. A clinical trial of this feasible combination therapy of these clinically available agents is warranted.

Irreversible electroporation (IRE) has been demonstrated as an effective local method for locally advanced (stage 3) pancreatic adenocarcinoma. Immune regulatory T cells (Tregs) induce immunosuppression of tumors by inhibiting patients’ anti-tumor adaptive immune response. This study aimed to evaluate the immunomodulation effect of IRE to identify an ideal time point for potential adjuvant immunotherapy. This study prospectively evaluated an institutional review board-approved study of patients undergoing either in situ IRE or pancreatectomy. Patient blood samples were collected at different time points (before surgery [preOP] and on postoperative day [POD] 1, POD3, and POD5). Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for three different CD4 + Treg subsets (CD25 + CD4 +, CD4 + CD25 + FoxP3 +, CD4 + CD25 + FoxP3 −) by flow cytometry and analyzed for median fold change (MFC) between each two consecutive time points (MFC = log2(T2/T1)). The study analyzed 15 patients with in situ IRE (n = 11) or pancreatectomy (PAN) (n = 4). In both groups, CD25 + CD4 + Tregs decreased on POD1 followed by a steady increase in pancreatectomy, whereas the trend in the IRE group reversed between D3 and D5 (MFC: IRE [− 0.01], PAN [+ 0.39]). For each period, CD4 + CD25 + FoxP3 + Tregs showed the most dramatic inverse effect, with D3 to D5 showing the most change (MFC: IRE [− 0.18], PAN [+ 0.39]). Also, CD4 + CD25 + FoxP3 − Tregs showed an inverse effect between D3 and D5 (MFC: IRE [− 0.25], PAN [+ 0.49]). Altogether, the Treg trend was inversely affected by the in situ IRE procedure, with the greatest cumulative significant change for all three Treg subsets between D3 and D5 (MFC ± SEM: IRE [− 0.24 ± 0.05], PAN [+ 0.37 ± 0.02]; p = 0.016). The study data suggest that in situ IRE procedure-mediated Treg attenuation between POD3 and POD5 can provide a clinical window of opportunity for potentiating clinical efficacy in combination with immunotherapy.

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

This study sought to evaluate re-excision rates, patient satisfaction with their breasts, and healthcare costs before and after publication of 2014 Society of Surgical Oncology/American Society of Radiation Oncology consensus guideline on margins for breast conserving operation with whole-breast irradiation for stage I and II breast cancer at an academic institution.Patients with stage I and II invasive carcinomas who underwent partial mastectomy were divided into 2 groups based on whether they were treated before (PRE) or after (POST) guideline publication in March 2014. Groups were compared with respect to re-excision rates, conversion to mastectomy, specimen volumes, mean cost per patient of surgical care, and prospectively collected patient post-procedure quality of life.A total of 237 patients who underwent partial mastectomy were examined (n = 126 in the PRE group and n = 111 in the POST group). Patients in the POST group were less likely to require re-excision (9% POST vs 37% PRE; p0.001) and were less likely to undergo conversion to mastectomy (5% POST vs 14% PRE; p = 0.02). After consensus guideline publication, mean operative cost per patient decreased ($4,874 POST vs $5,772 PRE; p0.001), and patients had improved breast quality of life scores (77 out of 100 POST vs 61 out of 100 PRE; p = 0.03). On multivariable analysis, publication of the consensus statement was an independent predictor of decreased re-excision rates (odds ratio 0.17; 95% CI 0.08 to 0.38; p0.001) and operative cost per patient (odds ratio 0.14; 95% CI 0.78 to 0.30; p0.001).Widespread implementation of the consensus guideline on margins for breast conserving operation will likely lead to the intended improvements in operative and financial outcomes, as well as patient satisfaction with breast conserving operation.

The aim of this study was to evaluate potential factors affecting the time period in which a 50 per cent parathyroid hormone (PTH) drop is observed. Eight-seven patients undergoing focused parathyroidectomy between 2011 and 2015, whose PTH values dropped to within normal range, were grouped according to whether they required > or ≤15 minutes after gland excision to achieve a 50 per cent PTH. Groups were compared according to preoperative PTH, calcium, age, glomer-ular filtration rate, and adenoma weight. Lower preoperative and preincision PTH levels were associated with requiring >15 minutes to achieve a >50 per cent drop in ioPTH. Time to >50 per cent ioPTH drop did not affect cure rates at one year, though a >15 minutes requirement was associated with higher serum calcium levels (P = 0.015). Lower baseline PTH and preincision PTH levels are significantly associated with a >15 minutes postexcision time to achieve a >50 per cent drop in ioPTH. Future analyses are warranted to determine whether a longer postexcision time threshold before proceeding with four-gland exploration is warranted in patients with primary hyperparathyroidism and mildly elevated preoperative PTH.

BACKGROUND AND OBJECTIVES Accurately assessing breast volume (BV) relative to the volume of breast tissue to be removed could help objectively determine the optimal surgical candidates for breast conserving surgery. The objective of this study was to determine the optimal mammography-based method of BV estimation. METHODS Mammography data was obtained for patients who underwent mastectomy for breast cancer from 2005 to 2015. This data was used to calculate BV using four previously published equations. Results were compared to mastectomy specimen volumes calculated from specimen weights and breast density. Five practitioners then independently assessed reproducibility and ease of use. RESULTS Complete mammographic measurements were available for 65 breasts from 45 patients. Median age was 58 years (range 19-82). Mammographic breast density scores were available for 62 breasts. Of the 65 mastectomies performed, 16 (36%) were simple mastectomies. The equation BV = 1/3πRcc Rmlo Hmlo most closely approximated actual breast specimen volumes (R = 0.89, P

Background The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma. Methods A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes. Results A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival. Conclusion Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.

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

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.

The essential diagnosis for LAPC is based on high-quality cross-sectional imaging, which demonstrates tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and non-thermal ablation modalities. This review will present the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer.

The optimal use of esophageal stents for malignant and benign esophageal strictures continues to be plagued with variability in pain tolerance, migration rates, and reflux-related symptoms. The aim of this study was to evaluate the differences in radial force exhibited by a variety of esophageal stents with respect to the patient’s esophageal stricture. Radial force testing was performed on eight stents manufactured by four different companies using a hydraulic press and a 5000 N force gage. Radial force was measured using three different tests: transverse compression, circumferential compression, and a three-point bending test. Esophageal stricture composition and diameters were measured to assess maximum diameter, length, and proximal esophageal diameter among 15 patients prior to stenting. There was a statistically significant difference in mean radial force for transverse compression tests at the middle (range 4.25–0.66 newtons/millimeter N/mm) and at the flange (range 3.32–0.48 N/mm). There were also statistical differences in mean radial force for circumferential test (ranged from 1.19 to 10.50 N/mm, p

Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This limitation is largely due to the relatively immunosuppressive environment surrounding the tumor. A focal ablative technique called irreversible electroporation (IRE) has been shown to modulate this environment, enhancing the efficacy of immunotherapy. One enhancing factor related to improved prognosis is a decrease in regulatory T cells (T-reg). This decrease has been previously unpredictable for clinicians using IRE, who currently have limited real-time metrics for determining the activation of the patient's immune response. Here, we report that larger overall changes in output current are correlated with larger decreases in T cell populations 24 hours post-treatment. This result suggests that clinicians can make real-time decisions regarding optimal follow-up therapy based on the range of output current delivered during treatment. This capability could maximize the immunomodulating effect of IRE in synergy with follow-up immunotherapy. Additionally, these results suggest that feedback from a preliminary IRE treatment of the local tumor may help inform clinicians regarding the timing and choice of subsequent therapies, such as resection, immunotherapy, chemotherapy, or follow-up thermal or non-thermal ablation. Cures Within Reach (PUJFSANY); PanCAN [16-65-IANN]; Bradley Fellowship; Department of Electrical and Computer Engineering at Virginia Tech This work was supported by Cures Within Reach (PUJFSANY). R.D. would also like to acknowledge PanCAN (16-65-IANN) for general support of his research. N.B. acknowledges the Bradley Fellowship and the Department of Electrical and Computer Engineering at Virginia Tech for financial support. The authors would also like to thank Timothy O'Brien for assistance with the data extraction, and Kenneth N. Aycock for input on the manuscript.

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

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

Yttrium-90 radioembolization is a hepatic intra-arterial-based therapy using glass- or resin-based microspheres as carriers to deliver high-dose radiation to tumors to maximize dose while minimizing collateral damage. This study aimed to compare the safety and efficacy of glass (TheraSphere) versus resin (Selective Internal Radiation Spheres, SIR-Spheres) Y-90 in the treatment of intrahepatic metastatic disease. A review of a prospectively collected, institutional review board-approved database was conducted to identify patients who underwent Y-90 therapy, excluding those with hepatocellular carcinoma (HCC). Of 119 patients, 79 received SIR-Spheres and 40 received TheraSphere therapy. For intrahepatic cholangiocarcinoma, mean survival was 10.6 months in the SIR-Spheres group compared to 29.2 months in the TheraSphere group (log-rank 0.05). In colorectal cancer (CRC), mean survival was 16.3 months for SIR-Spheres therapy and 26.8 for TheraSphere therapy (log-rank 0.097). There were no documented severe (grade 3) side effects in the TheraSphere group compared to 14 % of patients who experienced side effects in the SIR-Spheres group. TheraSphere microsphere appears superior to SIR-Spheres in treating non-HCC intrahepatic malignancy. However, patient selection and better multi-disciplinary care may play a role in these differences. Continued studies in combination therapies for all hepatic malignancies is critical to the long-term success and sustainability of Y-90 therapy.

Introduction Irreversible electroporation (IRE) utilizes short, high-voltage pulses to irreversibly permeabilize the cell membrane, resulting in apoptotic cell death. In addition to the irreversible zone, IRE creates a reversible zone that could be utilized for enhanced drug delivery. The hypothesis of this study is that a zone of reversible electroporation exists and allows for increased chemotherapy delivery. Methods Ten immunocompromised mice with orthotopic human pancreatic adenocarcinoma tumors (Panc1) were treated with either IRE between two doses of gemcitabine (15 mg/kg) (ECT) (N = 5) or gemcitabine alone (N = 5). Gemcitabine levels in the serum, liver, and pancreas were analyzed with liquid chromatography/mass spectrometry (LC/MS). Results Concentration of gemcitabine within reversibly electroporated pancreatic tissue was higher in mice receiving ECT compared to those receiving gemcitabine alone (13,567 ng/ml vs.4,126 ng/ml; P = 0.0009). Pancreatic gemcitabine levels were 5.52 and 5.96 times higher than liver and serum levels, respectively, in the ECT group compared to 2.85 and 2.53 times higher (P = 0.117, P = 0.058), respectively, in mice receiving gemcitabine alone. Conclusion IRE can potentially reduce local recurrence by allowing increased drug delivery to the tissue in the reversible electroporation zone. This holds significant potential in augmenting efficacy of gemcitabine in treatment of locally advanced and borderline resectable pancreatic adenocarcinoma. J. Surg. Oncol. 2016;114:181–186. © 2016 Wiley Periodicals, Inc.

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

Background We evaluated the performance of the Response Evaluation Criteria in Solid Tumor (RECIST), modified RECIST, and the European Association for the Study of Liver (EASL) guidelines and correlated them with survival in patients with metastatic colorectal cancer (mCRC) treated with locoregional therapy (LRT). Patients and Methods Our LRT registry was evaluated from 2008 to 2013. 228 mCRC patients were treated with LRT (91% drug-eluting beads, 9% radioembolization) were evaluated. Cox regression and Kaplan–Meier (KM) statistics were utilized for survival analysis. Results Excellent inter-rater agreement between EASL/mRECIST (κ = 905) was seen. Correlations between RECIST/mRECIST (κ = 0.638) and EASL/RECIST were weaker (κ = 0.638 and 0.598, respectively). There were significant differences in KM and Cox regression survivals between responders and nonresponders with all three methods (all P

Bile duct injury (BDI) is an uncommon but major complication of cholecystectomy that has a poorly defined magnitude of effect on hospital costs. This study sought to calculate the healthcare costs, length of stay, and discharge status associated with bile duct injury in patients undergoing cholecystectomy in the United States. The Premier Healthcare Database, which comprises hospital-billing records from over 700 hospitals in the United States, was queried for all patients undergoing cholecystectomy between January 2010 and March 2018. BDI was defined by ICD-9-CM and ICD-10-CM codes. Patient demographics, clinical characteristics, and operative information were extracted. Hospital costs, length of stay, and discharge status were compared between BDI and non-BDI patients. Propensity score matching was used to minimize confounding factors. Multivariable regression models were used to estimate the association between BDI and the outcomes variables. A total of 1,168,288 cholecystectomies were identified. BDI occurred in 878 patients (0.08%). Laparoscopy was the most common approach (> 95%). The majority of BDI occurred during inpatient admissions (71.0%). BDI patients had higher index admission hospital costs ($18,771 vs. $12,345, p

Appropriate postoperative readmission rates and modifiable risk factors for readmission have yet to be defined for many operations. This systematic review and meta-analysis attempt to define these parameters for pancreaticoduodenectomy.The main outcomes were readmission rate, risk factors, and reasons for readmission. Meta-analyses were performed when data was homogeneous, otherwise, a qualitative review was performed.The 30-day, 90-day, and overall readmission rates were 17.63%, 26.14%, and 27.18%, respectively. In the meta-analysis, chronic pancreatitis (OR, 1.44, p = 0.04), operative length (MD, 26.1; p 0.01), wound infection (OR, 1.9, p 0.01), intra-abdominal abscess (OR, 3.79, p 0.01), VTE (OR, 2.27, p = 0.01), and LOS (MD, 1.66, p 0.01) where associated with readmission.Hospital readmission will continue to be a quality metric and will influence reimbursement models. Thirty and 60-day readmission data underestimate the true readmission rate. Chronic pancreatitis, operative length, and several post-operative complications were associated with greater readmission. More uniform reporting is necessary to identify modifiable risk factors associated with readmission.

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.

Aim: To compare overall survival (OS) and liver cancer-specific survival (LCSS) in patients with localized hepatocellular carcinoma treated with surgical resection (SR) or thermal ablation (TA) using the Surveillance, Epidemiology and End Results database. Materials & methods: Kaplan–Meier, competing risk and Cox regression analyses were performed after identifying patients. Propensity score matching was then applied. Results: There was significantly better OS in the SR group and significantly lower probability of LCSS in the TA group. After matching, there was significantly longer OS in the SR group and a lower probability of LCSS in the TA group. Conclusion: SR offered a significant survival benefit over TA for localized hepatocellular carcinoma.

Data on prognostic implications of peri-operative blood transfusion around resection of colorectal cancer liver metastases (CRLM) are conflicting. This retrospective study assesses the association of transfusion with complications and disease-specific survival (DSS).Major hepatectomies for CRLM from 2000 to 2010 at three institutions were included. Transfusion was analyzed based on timing and volume.Of 456 patients, 140 (30.7%) received transfusions. Transfusion was associated with extended hepatectomy (28.6 vs 18.4%; p = 0.020), tumor size (5.7 vs 4.2 cm; p0.001), and operative blood loss (917 vs 390 mL; p0.001). Transfusion was independently associated with major complications (OR 2.61; 95% CI: 1.53-4.44; p0.001). Transfusion at any time was not associated with DSS; however, patients who specifically received blood post-operatively had reduced DSS (37.4 vs 42.7 months; p = 0.044). Increased volume of transfusion (≥3 units) was also associated with shortened DSS (Total: 37.4 vs 41.5 months, p = 0.018; Post-operative: 27.2 vs 40.3 months, p = 0.015). On multivariate analysis, however, transfusion was not independently associated with worsened DSS, regardless of timing and volume.Transfusion with major hepatectomy for colorectal cancer metastases is independently associated with increased complications but not disease-specific survival. Judicious use of transfusion per a blood utilization protocol in the peri-operative period is warranted.

Major (3 segments of the liver) or minor hepatectomy has been demonstrated to provide the most definitive chance for long-term remission and disease-free survival in hepatic malignancies. However, concerns remain in regards to the ability of the elderly (70 years old) and older (80 years old) patients to "tolerate" this type of resection. Thus, the aim of this study was to determine the short- and long-term effects of hepatectomies in the elderly patient population.An Institutional Review Board approved a prospectively maintained, single-institution HPB database with 663 consecutive hepatectomies from 2003 to 2013 was reviewed. Patients were separated into elderly (70 years old) and older. Short-term effects were defined as a 30-day morbidity/mortality, and long-term effects were defined as a 90-day morbidity/mortality and the ability to regain preoperative functional independence. Comorbidities were compared using the Charleston Comorbidity Index (CCI). The log-rank and Wilcoxon tests were used to evaluate postoperative outcomes.A total of 663 patients were reviewed, 480 70y/o, 183 were 70 or older, 104 were 75 or older, and 41 were 80 or older. Patients over 70, 75, and 80 years of age showed a higher incidence of preoperative comorbidities than younger patients when compared using CCI (P 0.05). Non-elderly patients had more liver lesions than elderly patients (median numbers only 3 vs. 1, P = 0.005). Patients over 70, 75, and 80 years old showed a higher 90-day mortality rate patients (11, 13, 17 %, respectively) to patients less than 70, 75 and 80 (3, 5, 5 %, respectively, P 0.05) (Table). Patients over 70, 75, and 80 years old showed increased morbidity (53, 57, 66 %, respectively) than patients less than 70, 75, and 80 (39, 34, 41 %, respectively, P 0.05). The severity of complication in elderly patients was similar to younger patients. Patients older than 70, 75, and 80 years showed an increased incidence of discharge to rehabilitation facilities (13, 15, 17 %, respectively) than patients less than 70, 75, and 80 (2, 3, 5 %, respectively, P = 0.001). Logistic regression demonstrated a significant risk of morbidity with an inability to return to preoperative function with a CCI 5, major hepatectomy, and75 years of age (HR 3.8, CI 2.1-5.6) CONCLUSIONS: This study demonstrates an increased rate of a 30- and 90-day postoperative mortality in75-year old patients. Permanent loss of preoperative function (i.e., ability to live independently or alone) remains a significant risk and a subset of older patients. Communicating this loss of function as well as morbidity/mortality is key to the informed consent process for older patients as well as their families.

Over the past several decades, there has been increasing discussion regarding the optimal management of secondary liver malignancies. Traditionally, resection has only been recommended if it could be accomplished with negative microscopic margins of at least 10 mm. However, many investigators have pushed this limit to offer resection to patients with narrower margins. We review the data regarding the impact of margin clearance on outcomes for patients undergoing hepatic metastasectomy. J. Surg. Oncol. © 2015 Wiley Periodicals, Inc.

Background The purpose of this study was to determine the impact of a restrictive blood transfusion protocol on the number of transfusions performed and the related effect on patient morbidity. Methods A cohort study was performed using our prospective database with information from January 1, 2000, to June 1, 2013. The restrictive blood transfusion protocol was implemented in September 2011, so this date served as the separation point for the date of operation criteria. Results For the study, 415 patients undergoing operation for an abdominal malignancy were reviewed. After the restrictive blood transfusion protocol, the percentage of patients who received blood dropped from 35.6% to 28.3%. The percentage of patients who experienced perioperative complication was significantly higher in transfused patients compared with those who did not receive blood ( P = .0001). There was no statistical significance observed between the 5 groups for the length of stay at the hospital after their procedure. Conclusions The restrictive blood transfusion protocol resulted in a reduction of the percentage of patients transfused, and there was no evidence to suggest that it negatively affected the outcomes of patients in this group.

Background Data are lacking on long-term outcomes of patients undergoing major hepatectomy requiring bile duct resection (BDR) for the treatment of colorectal cancer liver metastases. Methods Patients who underwent major hepatectomy (≥3 segments) for metastatic colorectal cancer from 2000–2010 at three US academic institutions were included. The primary outcome was disease-specific survival (DSS). Results Of 429 patients, nine (2.1%) underwent BDR, which was associated with pre-operative portal vein embolization (25.0% vs. 4.3%; P = 0.049). There were no significant differences in age, ASA class, margin status, number of lesions, tumor size, cirrhosis, perineural invasion, or lymphovascular invasion. BDR was independently associated with increased postoperative major complications (OR: 6.22; 95%CI:1.44–26.97; P = 0.015). There were no differences in length of stay, reoperation, readmission, or 30-day mortality. Patients who underwent BDR had markedly decreased DSS (9.3 vs. 39.9 mo; P = 0.002). When accounting for differences between the two groups, the need for BDR was independently associated with reduced DSS (HR: 3.06; 95%CI:1.12–8.34; P = 0.029). Conclusion Major hepatectomy with concomitant bile duct resection is seldom performed in patients undergoing resection of colorectal cancer liver metastases and is associated with higher major morbidity and reduced disease-specific survival compared to major hepatectomy alone. Stringent selection criteria should be applied when patients may need bile duct resection during hepatectomy for colorectal cancer liver metastases. J. Surg. Oncol. 2015; 112:524–528. © 2015 Wiley Periodicals, Inc.

BACKGROUND Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis. METHODS Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival. RESULTS The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months). CONCLUSIONS The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection. Cancer 2015. © 2015 American Cancer Society. Cancer 2015;121:3649–3658. © 2015 American Cancer Society.

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.

To compare outcomes of laparoscopic versus open hepatic resection (OHR) exclusively for hepatocellular carcinoma in terms of morbidity and cost. Laparoscopic hepatic resection (LHR) has become more prevalent with recent improvements in instrumentation and surgeon experience. A review of multicenter, prospectively collected hepatobiliary databases from three institutions was performed from 12/1990 to 12/2009. Prospective evaluation of all patients undergoing hepatectomy for hepatocellular cancer was performed. A total of 354 patients who had resections for Hepatocellular carcinoma (HCC) were analyzed, 100 were performed laparoscopically. The two groups were similar in terms of demographics and comorbidities. Evaluation of outcomes showed significantly higher intraoperative estimated blood loss although postoperative transfusion rates were similar. The incidence of any complication (44 vs 44 %, p = 0.23) and 90-day mortality (6 vs 6 %, p = 0.8) were similar between the two groups, with a similar reoperation rate (4.0 vs. 2.4 %; p = 0.9). Using Cox regression analysis, the laparoscopic approach had no effect on disease-free interval (OR 1.4, CI 0.31–6.3, p = 0.66) or overall survival (HR 1.2, CI 0.59–2.5 p = 0.6). Length of stay was significantly shorter in the laparoscopic group 6.2 vs. 9.3 days (p = 0.001). Adjusted operative charges ($41 vs. $39 k, p = 0.601) and adjusted total hospital charges ($71 vs. $82 k, p = 0.368) were similar in LHR versus OHR. Our study confirms previous literature showing comparable perioperative outcomes and recurrence. We further show comparable cost with laparoscopic versus open liver resection for HCC.

Management of anemia in surgical oncology patients remains one of the key quality components in overall care and cost. Continued reports demonstrate the effects of hospital transfusion, which has been demonstrated to lead to a longer length of stay, more complications, and possibly worse overall oncologic outcomes. The hypothesis for this study was that a dedicated restrictive transfusion protocol in patients undergoing hepatectomy would lead to less overall blood transfusion with no increase in overall morbidity.A cohort study was performed using our prospective database from January 2000 to June 2013. September 2011 served as the separation point for the date of operation criteria because this marked the implementation of more restrictive blood transfusion guidelines.A total of 186 patients undergoing liver resection were reviewed. The restrictive blood transfusion guidelines reduced the percentage of patients that received blood from 31.0% before January 9, 2011 to 23.3% after this date (P = .03). The liver procedure that was most consistently associated with higher levels of transfusion was a right lobectomy (16%). Prior surgery and endoscopic stent were the 2 preoperative interventions associated with receiving blood. Patients who received blood before and after the restrictive period had similar predictive factors: major hepatectomies, higher intraoperative blood loss, lower preoperative hemoglobin level, older age, prior systemic chemotherapy, and lower preoperative nutritional parameters (all P .05). Patients who received blood did not have worse overall progression-free survival or overall survival.A restrictive blood transfusion protocol reduces the incidence of blood transfusions and the number of packed red blood cells transfused. Patients who require blood have similar preoperative and intraoperative factors that cannot be mitigated in oncology patients. Restrictive use of blood transfusions can reduce cost and does adversely affect patients undergoing liver resection.

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.

Concerns remain over the ability to stent across of the lower esophageal sphincter (LES) for esophageal adenocarcinoma and the effects of gastroesophageal (GE) reflux. Thus, the aim of this study was to demonstrate minimal quality-of-life (QOL) side effects in patients undergoing esophageal stenting across the LES. An Institutional Review Board–approved prospective clinical trial evaluated the results of the Gastrointestinal Symptom questionnaire that includes a validated GE reflux disease (GERD) assessment (GERD-HRQL) and a dysphagia assessment. Consecutive patients were enrolled in this clinical trial, with 81 per cent male, 19 per cent female, median age of 62 years, with adenocarcinoma of the GE junction as their diagnosis. The median dysphagia score was 3 (only liquids can be tolerated) prestent and was improved to a median score of 0 (ability to eat all foods) poststent ( P = 0.01). The median GERD score was 0 (none) prestent and did not change with a median score of 0 (none) poststent ( P = 0.2). All GERD-related questions were unchanged prestent and poststent in all categories, specifically: frequency of GERD, time of day of reflux, pain behind breastbone, and pain medications. There was also no difference in regurgitation frequency (median prestent 1 vs poststent 0, P = 0.08), texture (prestent 2 [semisolid] vs poststent 1 [liquid]). There was only a statistical change in the ability to belch (prestent 0 [no ability] to poststent 1 [ability]), P = 0.02) and the ability to vomit. Esophageal stenting across the GE junction for dysphagia relief in esophageal malignancies does not adversely effect a patient's QOL in regard to reflux-related symptoms.

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.