Publications by authors named "Kiara Tulla"

21 Publications

  • Page 1 of 1

Combination Immunotherapy With LIGHT and Interleukin-2 Increases CD8 Central Memory T-Cells In Vivo.

J Surg Res 2021 Feb 22;263:44-52. Epub 2021 Feb 22.

Division of Surgical Oncology, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois. Electronic address:

Background: The generation of long-term durable tumor immunity and prolonged disease-free survival depends on the ability to generate and support CD8+ central memory T-cells. Microsatellite-stable colon cancer is resistant to currently available immunotherapies; thus, development of novel mechanisms to increase both lymphocyte infiltration and central memory formation are needed to improve outcomes in these patients. We have previously demonstrated that both interleukin-2 (IL-2) and LIGHT (TNFSF14) independently enhance antitumor immune responses and hypothesize that combination immunotherapy may increase the CD8+ central memory T-cell response.

Methods: Murine colorectal cancer tumors were established in syngeneic mice. Tumors were treated with control, soluble, or liposomal IL-2 at established intervals. A subset of animal tumors overexpressed tumor necrosis superfamily factor LIGHT (TNFSF14). Peripheral blood, splenic, and tumor-infiltrating lymphocytes were isolated for phenotypic studies and flow cytometry.

Results: Tumors exposed to a combination of LIGHT and IL-2 experienced a decrease in tumor size compared with IL-2 alone that was not demonstrated in wild-type tumors or between other treatment groups. Combination exposure also increased splenic central memory CD8+ cells compared with IL-2 administration alone, while not increasing tumor-infiltrating lymphocytes. In the periphery, the combination enhanced levels of circulating CD8 T-cells and central memory T-cells, while also increasing circulating T-regulatory cells.

Conclusions: Combination of IL-2, whether soluble or liposomal, with exposure to LIGHT results in increased CD8+ central memory cells in the spleen and periphery. New combination immunotherapy strategies that support both effector and memory T-cell functions are critical to enhancing durable antitumor responses and warrant further investigation.
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http://dx.doi.org/10.1016/j.jss.2021.01.010DOI Listing
February 2021

Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure.

Am J Transplant 2021 04 15;21(4):1525-1534. Epub 2020 Oct 15.

Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL.

Patients with obesity have limited access to kidney transplantation, mainly due to an increased incidence of surgical complications, which could be reduced with selective use of robotic-assisted surgery. This prospective randomized controlled trial compares the safety and efficacy of combining robotic sleeve gastrectomy and robotic-assisted kidney transplant to robotic kidney transplant alone in candidates with class II or III obesity. Twenty candidates were recruited, 11 were randomized to the robotic sleeve gastrectomy and robotic-assisted kidney transplant group and 9 to the robotic kidney transplant group. At 12-month follow-up, change in body mass index was -8.76 ± 1.82 in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group compared to 1.70 ± 2.30 in the robotic kidney transplant group (P = .0041). Estimated glomerular filtration rate, serum creatinine, readmission rates, and graft failure rates up to 12 months were not different between the two groups. Length of surgery was longer in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group (405 minutes vs. 269 minutes, p = .00304) without increase in estimated blood loss (120 ml vs. 117 ml, p = .908) or incidence of surgical complications. Combined robotic-assisted kidney transplant and sleeve gastrectomy is safe and effective compared to robotic-assisted kidney transplant alone.
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http://dx.doi.org/10.1111/ajt.16322DOI Listing
April 2021

Robotic Assisted Living Donor Nephrectomies: A Safe Alternative to Laparoscopic Technique for Kidney Transplant Donation.

Ann Surg 2020 Jul 9. Epub 2020 Jul 9.

Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Illinois.

Objective: To review outcomes after laparoscopic, robotic-assisted living donor nephrectomy (RLDN) in the first, and largest series reported to date.

Summary Of Background Data: Introduction of minimal invasive, laparoscopic donor nephrectomy has increased live kidney donation, paving the way for further innovation to expand the donor pool with RLDN.

Methods: Retrospective chart review of 1084 consecutive RLDNs performed between 2000 and 2017. Patient demographics, surgical data, and complications were collected.

Results: Six patients underwent conversion to open procedures between 2002 and 2005, whereas the remainder were successfully completed robotically. Median donor age was 35.7 (17.4) years, with a median BMI of 28.6 (7.7) kg/m. Nephrectomies were preferentially performed on the left side (95.2%). Multiple renal arteries were present in 24.1%. Median operative time was 159 (54) minutes, warm ischemia time 180 (90) seconds, estimated blood loss 50 (32) mL, and length of stay 3 (1) days. The median follow-up was 15 (28) months. Complications were reported in 216 patients (19.9%), of which 176 patients (81.5%) were minor (Clavien-Dindo class I and II). Duration of surgery, warm ischemia time, operative blood loss, conversion, and complication rates were not associated with increase in body mass index.

Conclusion: RLDN is a safe technique and offers a reasonable alternative to conventional laparoscopic surgery, in particular in donors with higher body mass index and multiple arteries. It offers transplant surgeons a platform to develop skills in robotic-assisted surgery needed in the more advanced setting of minimal invasive recipient operations.
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http://dx.doi.org/10.1097/SLA.0000000000004247DOI Listing
July 2020

Tracheostomy Following Liver Transplantation.

Transplant Proc 2020 Apr 2;52(3):932-937. Epub 2020 Mar 2.

Department of General Surgery, University of Illinois at Chicago, Chicago, IL.

Background: With increased demand for liver transplantation, sicker patients are being transplanted frequently. These patients are at a higher risk of significant postoperative morbidity, including respiratory failure. This study evaluated the phenotype that characterizes liver transplant candidates who may benefit from early tracheostomy.

Methods: A single center retrospective review of all liver transplant candidates between January 2012 and December 2017. Patients who eventually required tracheostomies were identified and compared to their counterparts.

Results: Of the 130 liver transplants performed during the study period, 11 patients required tracheostomy. Although patients in the tracheostomized population (TP) did not have significantly worse preoperative functional status (<4 metabolic equivalents; 64% vs 42%, P = .21), they had a higher native model for end-stage liver disease (MELD) score (37 vs 30, P < .05) at the time of transplantation. Patients who eventually succumbed to respiratory failure had lower arterial pressure of oxygen/fraction of inspired oxygen (PaO/FiO) ratios at the start of surgery and remained unchanged for the duration of surgery compared with the nontracheostomy group (P < .05). TP patients required more net fluid intraoperatively (7.3 vs 5.0 L, P < .05), increased length of time to attempted extubation (3.5 vs 1 day, P < .05), longer ventilation days (15 vs 1 day, P < .05), increased length of stay (37 vs 9 days, P < .05), and higher 1-year mortality (36% vs 8%, P < .05).

Conclusions: Based on our findings, patients with a high MELD score (>30), net postoperative fluid balance >6 L, and PaO/FiO ratio ≤300 who fail to wean off mechanical ventilation after 72 hours may benefit from tracheostomy during the postoperative period.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.009DOI Listing
April 2020

Geographic Disparities in Liver Allocation and Distribution in the United States: Where Are We Now?

Transplant Proc 2019 Dec 13;51(10):3205-3212. Epub 2019 Nov 13.

Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois.

Background: Equitable deceased donor liver allocation and distribution has remained a heated topic in transplant medicine. Despite the establishment of numerous policies, mixed reports regarding organ allocation persist.

Methods: Patient data was obtained from the United Network for Organ Sharing liver transplant database between January 2016 and September 2017. A total of 20,190 patients were included in the analysis. Of this number, 8790 transplanted patients had a median Model for End-Stage Liver Disease (MELD) score of 25 (17-33), after a wait time of 129 (32-273) days. Patients were grouped into low MELD and high MELD regions using a score 25 as the cutoff.

Results: Significant differences were noted between low and high MELD regions in ethnicity (white 77.4% vs 60.4%, Hispanic 8.1% vs 24.5%; P < .001) and highest level of education (grade school 4.8% vs 8.5%, Associate/Bachelor's degree 19% vs 15.7%, P < .001), respectively. Patients in high MELD regions were more likely to be multiply listed if they had a diagnosis of hepatocellular carcinoma (12.1% vs 15%, P = .046). Wait-list mortality (4.8% vs 6%, P < .001) and wait-list time (110 [27-238] vs 156 [42-309] days, P < .001) were greater in the high MELD regions.

Conclusions: These results highlight some of the existing disparities in the recently updated allocation and distribution policy of deceased donor livers. Our findings are consistent with previous work and support the liver distribution policy revision.
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http://dx.doi.org/10.1016/j.transproceed.2019.07.018DOI Listing
December 2019

Simultaneous recipient external iliac endarterectomy and renal transplant - a propensity score matched analysis.

Transpl Int 2020 03 2;33(3):321-329. Epub 2019 Dec 2.

Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, IL, USA.

Patients with end-stage renal disease and severe iliac atherosclerosis are frequently denied renal transplant due to technical challenges, and risk of potential steal syndrome in the allograft, or ipsilateral limb. Few studies have evaluated the safety and efficacy of performing an endarterectomy in this setting. A single-center retrospective review of renal transplant patients from 1/2013 to 12/2017 was performed. Patients requiring endarterectomy at the time of transplant were matched to a nonendarterectomized cohort in a 1:2 fashion using propensity score matching. Patients were followed for a minimum of 12 months. Simultaneous endarterectomy and renal transplant were performed in 23 patients and subsequently matched to 42 controls. Ankle-brachial index was lower in the endarterectomized group (P = 0.04). Delayed graft function (26.1% vs. 19%, P = 0.54), graft loss (8.7% vs. 7.1%, P = 0.53), 1-year mortality (8.7% vs. 4.8%, P = 0.53), and renal function at 12 months were comparable in both groups. There were no incidents of ipsilateral limb loss in the endarterectomized population. This is the first matched study investigating endarterectomy and renal transplant. Long-term follow-up of limb and graft function is indicated. Despite the small sample size, our findings suggest that a combined procedure can safely provide renal transplantation access to a previously underserved population.
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http://dx.doi.org/10.1111/tri.13559DOI Listing
March 2020

Indications of Intestinal Transplantation.

Gastroenterol Clin North Am 2019 12 4;48(4):575-583. Epub 2019 Oct 4.

Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Suite 402, Chicago, IL 60612, USA. Electronic address:

"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and availability of the donor organs, and specialized care. Combined liver and intestinal transplant allows for patients who have parenteral nutrition-associated liver disease a possibility of improved quality of life and nutrition as well as survival. Intestinal transplantation has made giant strides over the past few decades to the present era where current graft survivals are comparable with other solid organ transplants."
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http://dx.doi.org/10.1016/j.gtc.2019.08.010DOI Listing
December 2019

Robotic kidney transplantation in the obese patient: 10-year experience from a single center.

Am J Transplant 2020 02 24;20(2):430-440. Epub 2019 Dec 24.

Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois.

Despite increasing obesity rates in the dialysis population, obese kidney transplant candidates are still denied transplantation by many centers. We performed a single-center retrospective analysis of a robotic-assisted kidney transplant (RAKT) cohort from January 2009 to December 2018. A total of 239 patients were included in this analysis. The median BMI was 41.4 kg/m , with the majority (53.1%) of patients being African American and 69.4% of organs sourced from living donors. The median surgery duration and warm ischemia times were 4.8 hours and 45 minutes respectively. Wound complications (mostly seromas and hematomas) occurred in 3.8% of patients, with 1 patient developing a surgical site infection (SSI). Seventeen (7.1%) graft failures, mostly due to acute rejection, were reported during follow-up. Patient survival was 98% and 95%, whereas graft survival was 98% and 93%, at 1 and 3 years respectively. Similar survival statistics were obtained from patients undergoing open transplant over the same time period from the UNOS database. In conclusion, RAKT can be safely performed in obese patients with minimal SSI risk, excellent graft function, and patient outcomes comparable to national data. RAKT could improve access to kidney transplantation in obese patients due to the low surgical complication rate.
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http://dx.doi.org/10.1111/ajt.15626DOI Listing
February 2020

The utility of robotic assisted pancreas transplants - a single center retrospective study.

Transpl Int 2019 Nov 1;32(11):1173-1181. Epub 2019 Aug 1.

Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA.

The prevalence of obesity within the diabetic population is on the rise. This development poses unique challenges for pancreas transplantation candidates as obese individuals are often denied access to transplant. The introduction of robotic approach to transplant has been shown to improve outcomes in obese patients. A single center retrospective review of pancreas transplant cases over a 4-year period ending December 2018 was performed. Patients undergoing robotic surgery were compared to their counterparts undergoing open transplant. 49 patients (10 robot, 39 open) received pancreas transplants over the study period. Mean age was 43.1 ± 7.5 vs. 42.8 ± 9.7 years. There were no significant differences in demographics except body mass index (33.7 ± 5.2 vs. 27.1 ± 6.6, P = 0.005). Operative duration (7.6 ± 1.6 vs. 5.3 ± 1.4, P < 0.001), and warm ischemia times [45.5 (IQR: 13.7) vs. 33 (7), P < 0.001] were longer in the robotic arm. There were no wound complications in the robotic approach patients. Graft (100% vs. 88%, P = 0.37) and patient survival (100% vs. 100%, P = 0.72) after 1 year were similar. Our findings suggest that robotic pancreas is both safe and effective in obese diabetic patients, without added risk of wound complications. Wide adoption of the technique is encouraged while long term follow-up of our recipients is awaited.
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http://dx.doi.org/10.1111/tri.13477DOI Listing
November 2019

The impact of BMI extremes on disease-free survival and overall survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

J Gastrointest Oncol 2019 Apr;10(2):194-202

Division of Surgical Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are increasingly being offered to patients with peritoneal carcinomatosis (PC). On the other hand, the prevalence of obesity is also increasing and expected to reach unprecedented rates in the upcoming decades. Therefore, managing patients on either extreme of the body mass index (BMI) range is anticipated to become a routine challenge and it becomes imperative to understand the impact of BMI, as a spectrum, on the long-term outcomes of CRS and HIPEC. We aim to study the short and long-term outcomes of CRS and HIPEC in patients on both extremes of the BMI spectrum.

Methods: Patients with PC who underwent CRS and HIPEC over 10 years for ovarian, colorectal, and pseudomyxoma peritonei (PMP), and whose BMI was recorded were retrospectively included. Patients were divided based on their weight strata. The primary outcomes were disease-free survival (DFS) and overall survival (OS).

Results: A total of 126 patients were included. Fifty-seven point one percent were females and mean age was 59.31±1.57 years. No difference was noted between the groups in regards to demographics, perioperative characteristics, and immediate postoperative outcomes. Underweight group had a trend toward a higher peritoneal cancer index and lower rates of complete cytoreduction. Optimum BMI for OS and DFS was in the obesity range in colorectal PC, in the overweight range in ovarian PC, and in borderline obesity in PMP. Regression analysis identified underweight as an independent risk factor for shorter DFS, whereas underweight and morbid obesity were risk factors for shorter OS, after adjustment for other factors such as incomplete cytoreduction, tumor histology, and grade.

Conclusions: OS and DFS vary across the BMI strata. Ovarian PC demonstrates earlier recurrence and shorter survival, whereas colorectal PC demonstrates the "obesity paradox" as patients move into the realm of obesity. BMI extremes, low or high, generally carry a poor prognosis for OS.
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http://dx.doi.org/10.21037/jgo.2018.12.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465483PMC
April 2019

MADD silencing enhances anti-tumor activity of TRAIL in anaplastic thyroid cancer.

Endocr Relat Cancer 2019 06;26(6):551-563

Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois, USA.

ATC is an aggressive disease with limited therapeutic options due to drug resistance. TRAIL is an attractive anti-cancer therapy that can trigger apoptosis in a cancer cell-selective manner. However, TRAIL resistance is a major clinical obstacle for its use as a therapeutic drug. Previously, we demonstrated that MADD is a cancer cell pro-survival factor that can modulate TRAIL resistance. However, its role, if any, in overcoming TRAIL resistance in ATC is unknown. First, we characterized ATC cell lines as either TRAIL resistant, TRAIL sensitive or moderately TRAIL sensitive and evaluated MADD expression/cellular localization. We determined the effect of MADD siRNA on cellular growth and investigated its effect on TRAIL treatment. We assessed the effect of combination treatment (MADD siRNA and TRAIL) on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. The effect of combination treatment on tumor growth was assessed in vivo. We found increased levels of MADD in ATC cells relative to Nthy-ori 3-1. MADD protein localizes in the cytosol (endoplasmic reticulum and Golgi body) and membrane. MADD knockdown resulted in spontaneous cell death that was synergistically enhanced when combined with TRAIL treatment in otherwise resistant ATC cells. Combination treatment resulted in a significant reduction in MMP and enhanced generation of ROS indicating the putative mechanism of action. In an orthotopic mouse model of TRAIL-resistant ATC, treatment with MADD siRNA alone reduced tumor growth that, when combined with TRAIL, resulted in significant tumor regressions. We demonstrated the potential clinical utility of MADD knockdown in sensitizing cells to TRAIL-induced apoptosis in ATC.
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http://dx.doi.org/10.1530/ERC-18-0517DOI Listing
June 2019

Loss of MADD expression inhibits cellular growth and metastasis in anaplastic thyroid cancer.

Cell Death Dis 2019 02 13;10(2):145. Epub 2019 Feb 13.

Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, 60612, USA.

Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, explored its effect on cellular proliferation and metastases and examined its therapeutic potential in an orthotopic ATC model in athymic nude mice. When compared to untreated control and scramble siRNA, MADD siRNA treatment inhibited the proliferative capacity of 8505C, C643 and HTH7 cells in vitro and 8505C-derived-orthotopic tumor growth in vivo. MADD ablation caused a significant reduction in cellular migration and invasion potential; clonogenic capacity; as well as, mitochondrial length and potential in vitro. This MADD siRNA-induced anti-migratory/invasive effect corresponded with inhibition of epithelial-mesenchymal transition (EMT) and Wnt signaling. Mechanistically, MADD siRNA inhibited TNFα induced activation of pERK, pGSK3β and β-catenin, suggesting that MADD knockdown might exert its anti-migratory/invasive effects, by blocking TNFα/ERK/GSK3β axis. MADD siRNA can inhibit β-catenin nuclear translocation and consequently, the expression of its target genes in ATC cells. In in vivo experiments, along with tumor regression, MADD siRNA treatment also decreased evidence of lung metastases. Immunohistochemically, MADD siRNA-treated tumor tissues exhibited a reduction in Ki67 and N-Cadherin expression, and an increase in E-Cadherin expression. In conclusion, we show the crucial role of MADD in ATC tumorigenesis and metastasis and its potential implications as a molecular target for ATC therapy.
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http://dx.doi.org/10.1038/s41419-019-1351-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374448PMC
February 2019

A Simplified Peritoneal Sarcomatosis Score for patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

J Gastrointest Oncol 2018 Dec;9(6):1138-1143

Division of Surgical Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA.

Background: With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), long-term survival can be achieved in selected patients with peritoneal surface malignancy. In patients with peritoneal sarcomatosis (PS), CRS/HIPEC remains a topic of debate. It is important that patient selection and outcome be improved with a tool that better predicts survival in such patients. To this end, we devised a Simplified Peritoneal Sarcomatosis Score (SPSS) adopted from the previously-described peritoneal surface disease severity score (PSDSS).

Methods: Patients were included if they were diagnosed with PS and underwent CRS/HIPEC with intended complete cytoreduction between 2007 and 2017. To calculate SPSS, we recorded symptoms (none =0, present =1), peritoneal carcinomatosis index (PCI) (≤10=0, >10=1), and grade of tumor (low =0, high =1). Thus, SPSS ranged from 0 to 3. SPSS-L (low) included patients with score of 0-1; SPSS-H (high) included patients with scores 2-3. Survival curves were generated using Kaplan-Meier method according to the two tiers of SPSS.

Results: Twenty-five patients were included. Mean age was 51.84±10.75 years. Median follow-up was 18 months. Compared to SPSS-H, SPSS-L patients had a longer median overall survival (OS) (36±16 16±6 months, respectively; P=0.021) and a longer median disease-free survival (DFS) (36±16 16±6 months, respectively; P<0.001). On multivariate analysis, advanced disease (SPSS-H) was an independent predictor of OS (P=0.020) and DFS (P=0.018).

Conclusions: SPSS can be used as a tool for patient selection for surgery, prognosis prediction, and stratification into clinical trials of PS patients.
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http://dx.doi.org/10.21037/jgo.2018.08.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286947PMC
December 2018

Vaccination With Mitoxantrone-Treated Primary Colon Cancer Cells Enhances Tumor-Infiltrating Lymphocytes and Clinical Responses in Colorectal Liver Metastases.

J Surg Res 2019 01 17;233:57-64. Epub 2018 Aug 17.

Division of Surgical Oncology, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois. Electronic address:

Background: Colorectal cancer remains a leading cause of cancer-related mortality worldwide. Metastases to the liver are often present at initial presentation and will form in most patients during their course of disease. We have previously demonstrated that enhanced trafficking and activation of tumor-infiltrating lymphocytes in colorectal liver metastases (CRLM) may improve antitumor immune responses. Thus, development of novel mechanisms to increase lymphocyte infiltration and activation are needed to improve patient outcomes.

Methods: CT26 murine colorectal cancer cells were treated with physiologic levels of the potent inducer of immunogenic cell death mitoxantrone (MTX). An in situ vaccine was created with treated cells in an established model of CRLM. Cells were evaluated by flow cytometry for cell cycle evaluation and calreticulin expression. Splenic and tumor-infiltrating lymphocytes were isolated for phenotypic studies.

Results: MTX-treatment of colon cancer cells resulted in a sub-G1 peak, inhibition of G1 cell cycle progression, and increased G2/M cell fractions while simultaneously increasing dynamic exposure of calreticulin on the cell surface (P < 0.05). Vaccination with MTX-treated cells resulted in significant decreases in CRLM formation associated with increased tumor-infiltrating leukocytes that displayed increased expression of the T cell surface activation marker CD69.

Conclusions: Vaccination with MTX-treated primary colon cancer cells enhances tumor-infiltrating lymphocytes and clinical responses in CRLM.
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http://dx.doi.org/10.1016/j.jss.2018.07.068DOI Listing
January 2019

Therapeutic advances in anaplastic thyroid cancer: a current perspective.

Mol Cancer 2018 10 23;17(1):154. Epub 2018 Oct 23.

Department of Microbiology and Immunology, University of Illinois-College of Medicine, Chicago, IL, USA.

Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. In 2017, it was the fifth most common cancer in women. Although the majority of thyroid tumors are curable, about 2-3% of thyroid cancers are refractory to standard treatments. These undifferentiated, highly aggressive and mostly chemo-resistant tumors are phenotypically-termed anaplastic thyroid cancer (ATC). ATCs are resistant to standard therapies and are extremely difficult to manage. In this review, we provide the information related to current and recently emerged first-line systemic therapy (Dabrafenib and Trametinib) along with promising therapeutics which are in clinical trials and may be incorporated into clinical practice in the future. Different categories of promising therapeutics such as Aurora kinase inhibitors, multi-kinase inhibitors, epigenetic modulators, gene therapy using oncolytic viruses, apoptosis-inducing agents, and immunotherapy are reviewed. Combination treatment options that showed synergistic and antagonistic effects are also discussed. We highlight ongoing clinical trials in ATC and discuss how personalized medicine is crucial to design the second line of treatment. Besides using conventional combination therapy, embracing a personalized approach based on advanced genomics and proteomics assessment will be crucial to developing a tailored treatment plan to improve the chances of clinical success.
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http://dx.doi.org/10.1186/s12943-018-0903-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198524PMC
October 2018

Acute kidney injury increases the rate of major morbidities in cytoreductive surgery and HIPEC.

Ann Med Surg (Lond) 2018 Nov 26;35:163-168. Epub 2018 Sep 26.

Division of Surgical Oncology, Edward Hospital Cancer Center, Naperville, IL, USA.

Introduction: Acute kidney injury (AKI) following cardiovascular surgery has been shown to increase costs and overall morbidity and mortality. The incidence, risk factors, and outcomes of AKI following other types of major surgeries have not been as well characterized. We sought to study the incidence of AKI following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) per the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

Materials And Methods: Patients undergoing CRS and HIPEC between 2013 and 2015 were included. Demographic and perioperative data were compared between patients who experienced AKI versus controls using appropriate statistical analysis between categorical and continuous variables. AKI was recorded by a Certified Professional in Healthcare Quality (CPHQ) and defined as a rise in serum creatinine by ≥ 0.3 mg/dL within 48 h (KDIGO criteria).

Results: Fifty-eight consecutive patients undergoing CRS and HIPEC were included. Twelve (20.7%) patients were recorded to develop AKI. This was the most common complication recorded by the CPHQ member. There was one 30-day mortality secondary to cerebral infarction. AKI patients had a longer hospitalization period (14.2 ± 6.9 vs. 9.5 ± 3.3 days, p = 0.002), and a higher rate of major complications (50.00% vs. 15.21%; p = 0.018). Readmission rate was similar (p = 0.626). Multivariate regression identified excessive blood loss during surgery as a major predictor of AKI occurrence, and pre-existing comorbidities and postoperative AKI as predictors of major morbidities following CRS and HIPEC.

Conclusion: AKI following CRS and HIPEC appears to be a common complication which is associated with further major morbidities. Current quality improvement programs may be under-reporting this incidence.
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http://dx.doi.org/10.1016/j.amsu.2018.09.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178214PMC
November 2018

Living Donor Intestinal Transplantation.

Gastroenterol Clin North Am 2018 Jun 4;47(2):369-380. Epub 2018 Apr 4.

Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Suite 402, Chicago, IL 60612, USA.

Living donor intestinal transplantation (LDIT) has been improved leading to results comparable to those obtained with deceased donors. LDIT should be limited to specific indications and patient selection. The best indication is combined living donor intestinal/liver transplantation in pediatric recipients with intestinal and hepatic failure; the virtual elimination of waiting time may avoid the high mortality experienced by candidates on the deceased waiting list. Potentially, LDIT could be used in highly sensitized recipients to allow the application of de-sensitization protocols. In the case of available identical twins or HLA-identical sibling, LDIT has a significant immunologic advantage and should be offered.
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http://dx.doi.org/10.1016/j.gtc.2018.01.008DOI Listing
June 2018

Living Donor Liver Transplantation: Technical Innovations.

Gastroenterol Clin North Am 2018 Jun;47(2):253-265

Department of Surgery, Tulane University, 1415 Tulane Avenue, #HC-5, New Orleans, LA 70112-2632, USA. Electronic address:

Living donor liver transplantation (LDLT) has found a place to serve the end-stage liver disease community as the donor safety and recipient suitability has been elucidated. Donor safety is of paramount importance and transplant programs must continue endeavors to maintain the highest possible standards. At the same time, adequacy of grafts based on recipient clinical status via their model for end-stage liver disease (MELD) score and volumetric studies to achieve a GRBWR >0.8, along with special attention to anatomic tailoring and portal venous flow optimization are necessary for successful transplantation. Technical innovations have improved sequentially the utility and availability of LDLT.
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http://dx.doi.org/10.1016/j.gtc.2018.01.001DOI Listing
June 2018

The impact of chemotherapy and its timing on survival in malignant peritoneal mesothelioma treated with complete debulking.

Med Oncol 2018 Apr 12;35(5):69. Epub 2018 Apr 12.

Department of Surgical Oncology, Edward Cancer Center, Naperville, IL, USA.

The current standard of treatment for malignant peritoneal mesothelioma (MPM) is cytoreductive surgery when the disease distribution is favorable. The role of chemotherapy, as an adjunct to surgery, remains unclear. The national database of mesothelioma was used to identify MPM patients who were treated with curative intent. Patients were divided into treatment groups: (1) chemotherapy only, (2) surgery only, (3) neoadjuvant chemotherapy + surgery, and (4) surgery + adjuvant chemotherapy. A negative control group of patients who did not receive any treatment was added (group 0). Totally, 1740 patients were included. Mean age was 63.04 ± 14.58 and 60.7% were males. The patients' distribution into the treatment groups was 604, 684, 169, 55, and 228 patients in groups 0-4, respectively, with a median survival of 3.61 ± 0.37, 11.10 ± 0.73, 57.41 ± 11.91, 52.30 ± 7.20, and 55.00 ± 9.19 months. The addition of chemotherapy, in any setting, to surgery provided an improved survival at 1 year (p = 0.006). This survival benefit ceased at the 2-, 3-, and 5-year checkpoints. The multivariate analysis identified age, sarcomatoid/biphasic histologies, nodal and distant metastasis, and offering no treatment or chemotherapy only as poor prognostic factors for overall survival. No difference in overall survival was noted with the addition of chemotherapy to complete debulking regardless of the timing. Complete debulking remains the standard treatment for MPM. The addition of systemic chemotherapy provides a short-term survival improvement at 1 year only and was similar whether given in the neoadjuvant or adjuvant setting. Nevertheless, it did not add a survival benefit beyond the 1-year time point.
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http://dx.doi.org/10.1007/s12032-018-1125-4DOI Listing
April 2018

Attending Physician Remote Access of the Electronic Health Record and Implications for Resident Supervision: A Mixed Methods Study.

J Grad Med Educ 2017 Dec;9(6):706-713

Background : Advances in information technology have increased remote access to the electronic health record (EHR). Concurrently, standards defining appropriate resident supervision have evolved. How often and under what circumstances inpatient attending physicians remotely access the EHR for resident supervision is unknown.

Objective : We described a model of attending remote EHR use for resident supervision, and quantified the frequency and magnitude of use.

Methods : Using a mixed methods approach, general medicine inpatient attendings were surveyed and interviewed about their remote EHR use. Frequency of use and supervisory actions were quantitatively examined via survey. Transcripts from semistructured interviews were analyzed using grounded theory to identify codes and themes.

Results : A total of 83% (59 of 71) of attendings participated. Fifty-seven (97%) reported using the EHR remotely, with 54 (92%) reporting they discovered new clinical information not relayed by residents via remote EHR use. A majority (93%, 55 of 59) reported that this resulted in management changes, and 54% (32 of 59) reported making immediate changes by contacting cross-covering teams. Six major factors around remote EHR use emerged: resident, clinical, educational, personal, technical, and administrative. Attendings described resident and clinical factors as facilitating "backstage" supervision via remote EHR use.

Conclusions : In our study to assess attending remote EHR use for resident supervision, attendings reported frequent remote use with resulting supervisory actions, describing a previously uncharacterized form of "backstage" oversight supervision. Future work should explore best practices in remote EHR use to provide effective supervision and ultimately improve patient safety.
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http://dx.doi.org/10.4300/JGME-D-16-00847.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734323PMC
December 2017

Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

Langenbecks Arch Surg 2018 Mar 7;403(2):151-194. Epub 2017 Dec 7.

Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia.

Methods: A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines.

Results: Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia.

Conclusions: Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.
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http://dx.doi.org/10.1007/s00423-017-1644-zDOI Listing
March 2018