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Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.

Since the first successful total pancreatectomy with islet autotransplant (TPIAT) for the treatment of chronic pancreatitis some 40 years ago, the procedure has finally gained more widespread acceptance as the only reliable and effective treatment option to preserve endocrine pancreatic function and improve or cure the associated chronic pain syndrome. TPIAT is a complex procedure with a wide range of potential complications that are intrinsic to its two components: total pancreatectomy (TP) and islet autotransplantation (IAT). Mounting evidence in the literature supports TPIAT as an approach that can be done safely at centers with experience using open, laparoscopic, and/or robotic techniques with little or no morbidity and mortality. From the surgical perspective, the procedure is standardized and can be safely performed in adult and pediatric patients with chronic pancreatitis.

The pancreas was the first extrarenal organ that was successfully transplanted from a living donor in 1979. The objective of the procedure is to cure diabetes mellitus and to achieve insulin independence and normoglycemia. In the pre-calcineurin inhibitor era, LD pancreas transplantation offered improved graft survival compared to deceased donor transplants. In the calcineurin inhibitor era, this difference is hardly existent anymore and pancreas transplants from living donors are only performed in the presence of at least 1-haplotype human leukocyte antigen (HLA)-matches, high antibody [panel reactive antibody (PRA)] levels and need for low-dose immunosuppression. With improvements in surgical techniques, anticoagulation and immunosuppression, a living donor pancreas transplant remains a treatment option in selected patients due to elimination of waiting time, decreased rejection rates, and low-dose immunosuppression. Removal and transplantation of a living donor hemi-pancreas using the pancreatic tail with the splenic vessels can be accomplished with a very low surgical risk to both donor and recipient.

The technical aspects of pancreas transplantation are both challenging and complex. From the first clinical pancreas transplant in 1966 by Kelly and Lillehei at the University of Minnesota over the first segmental living donor pancreas transplant in 1979 to robotically performed pancreas transplants in the current era, pancreas transplantation has evolved with many technical modifications over the past 50 years at a steep pace. While 1-year mortality rates in the first two decades were as high as 30% and 1-year graft failure rates as high as 80%, current 1-year mortality rates are

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations.Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized “The Cancer Genome Atlas” (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic of effector T helper cell (Th) subsets by ELISA using plasma from each AA and CA participant.Results: Colon tumors from AA patients showed significant fold-change increase in gene expression when compared to CA for FOXP3 (6.22 vs. 3.22), IL1B (103 vs. 11.4) and IL8 (220 vs. 28.9) (p < 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and the immunotherapy targets PDL1 (CD274) and CTLA4 (p < 0.05). TCGA data validated our observed higher gene expression of GZMB and PDL1 in CA patients when compared to AA. Notably, our observations on immune cell populations show that AA tumors have significantly higher number of exhausted CD8+ cells (p < 0.01), mast cells (p < 0.02) and increased T regulatory cells when compared to CA. AA colon cancer patients differed from CA in cytokine production patterns in plasma (i.e., reduced IL-12).Conclusions: Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches.

The dawn of the era of single incision minimally invasive surgery, or single port surgery, was first realized with laparoscopy. Beginning with simple procedures surgeons began to apply this concept to a growing variety of procedures. Despite demonstrating its feasibility and associated favorable patient outcomes, single port laparoscopy remained a challenging procedure and was unsuccessful in gaining significant traction. With the addition of the robotic surgery, single port surgery was dramatically changed. With the aid of the robotic platform, surgeons were able to overcome the challenges and limitations of laparoscopy. Since the first reports of robotic assisted single port surgery in 2009, surgeons across all specialties and subspecialties have found application in their practice. In this review, we highlight the last decade of single site robotic surgery and discuss the current challenges.

Colorectal cancer (CRC) is the third most common cancer among African Americans (AA) and when compared to Caucasian Americans (CA), they present more advanced CRC disease and lower survival rates. Recent findings suggest that this may be related to the differential expression in genes linked to inflammation and immune response. Therefore, we aimed to investigate if tumors from AA colon cancer patients diverge in their immunologic profile from CA and if the immune response of a CRC cell line derived from an AA tumor will differ from a CA CRC cell line. Additionally, we are recording the genetic profiles of colon tumors and outcomes from AA patients at our institution. Methods: Using DESeq2 we evaluated the differential gene expression pattern by whole transcriptome sequencing (Illumina) of 10 CRC tissues (and matching adjacent non-tumor tissue) from both AA and CA individuals. We focused on genes involved in immune checkpoints and inflammation. We also examined the secretion of Interleukin 8 (IL-8) in plasma from our AA CRC patients. For the in vitro experiments, we used the AA tumor-derived colon cancer cell line SB-521, generated in Dr. Williams' laboratory, and the CA colon cancer cell line HT-29 to determine if the cell lines expressed the Programmed death-ligand 1 (PD-L1). Lastly, we analyzed the microsatellite (MSI) status and MMR mutations in tumors from AA colon cancer patients at our institution and correlated their genetic analysis to response to chemotherapies and survival. Results: The genomic data revealed that AA and CA tumors had a significant difference of expression in a total of 221 genes. Remarkably, some of these genes included PD1, IL1B, IL17A, IL10, IL5, CD80 and FOXP3. The cytokine IL-8 concentration detected by ELISA in plasma of these patients revealed a differential expression between early stages (I, II) and late stages (III, IV). As hypothesized, the MSI and AA tumor-derived cell line SB-521 expressed PD-L1 and showed an increase in protein levels in response to TNF-α treatment (the CA cell line HT-29 did not express PD-L1). Lastly, our retrospective data (N=200 patients) demonstrated that up to 20% of our AA colon cancer patients have MSI and/or MMR mutations. Conclusions: Altogether, our results suggest that the immune profiles of the tumors from AA patients differ from CA and these differences could be used as biomarkers and to guide therapeutic strategy for these populations. Also, since the AA cell line presented distinct inflammatory patterns and when compared to the HT-29 CA cell line, it is a potential model to study MSI and PD-L1 in AA. Hence, we aim to supplement our preliminary data on AA patients with MSI and MMR mutations at Downstate and to elucidate what other genomic differences exist and cytokines' secretion patterns observed. In conclusion, we will address the immune and molecular biology of CRC tumors in AA through genomic and in vitro studies, and generate patient's data on AA diagnosed with colon cancer. Citation Format: Jenny E. Paredes, Ping Ji, Maria Munoz-Sagastibelza, Sayed Imtiaz, Kaylene Barrera, Raavi Gupta, Maksim Agaronov, Henry Talus, Jovanny Zabaleta, Jennie Williams, Laura Martello-Rooney. Immune checkpoints and inflammation in colon tumors from African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 646.

Background and objectives Ventral hernia repair is one of the most commonly performed general surgery procedures, and minimally invasive approaches are increasingly preferred. The physiologic repair offered by the preperitoneal approach is favorable, with reduced complications, but it remains a technical challenge. The robotic platform allows for enhanced instrument flexibility and ease of operation. We conducted a retrospective review of our experience with robotic transabdominal preperitoneal repair (rTAPP) versus robotic intraperitoneal onlay mesh (rIPOM) at a tertiary care hospital in an urban setting. Methods We reviewed the records of patients undergoing minimally invasive ventral hernia repair from March 2014 through March 2017. Demographics, complication rates, and operative time were compared by t test and Chi square test, as applicable. Results Sixty-three patients met the criteria for inclusion in the study. Of those, 27 underwent ventral hernia repair with rIPOM and 36 with rTAPP, with no major intraoperative complications. There were no significant differences in demographics between the 2 groups in age, BMI, and sex. The difference in mean operative time was not significant (rIPOM 167.26 [SD 51.76] minutes vs rTAPP 158.84 minutes [SD 61.5]; P = .57), whereas mean console time was significantly different (rIPOM 70.88 minutes [SD 32.88] vs rTAPP 90.26 [SD 31.17]; P = .018). Postoperative complications occurred only with rIPOM and included urinary retention, seroma, and fever. Conclusions rTAPP is a promising alternative to rIPOM, with reduced complications without adding significant operative time, and may allow for reduced costs.

BACKGROUND: The aim of this study was to investigate a novel resident education model that turns the traditional surgical hierarchy upside down, termed a ‘‘reverse’’ peer-assisted learning curriculum. METHODS: Thirty surgical topics were randomized between medical students and chief residents on each clinical team, with 1 topic being presented briefly during morning rounds. An exam evaluating junior residents’ knowledge of these topics was administered before and after 1 month of presentations. A questionnaire was distributed to evaluate the junior residents’ perceptions of this teaching model. RESULTS: Thirty-four residents participated. There was a significant improvement in the mean examination score (54 vs 74, P , .05). No significant difference was noted in the mean score differentials of topics presented by either the medical students or the chief resident (21 vs 18, P 5.22). More than 80% of the residents responded positively about the effectiveness of this exercise and agreed that they would like to see this model used on other services. CONCLUSIONS: This study confirms the hypothesis that medical students can teach surgical topics to junior residents at least as effectively as their chief residents. Published by Elsevier Inc.

In contrast to adult colonic intussusception in which malignancy is the dominant cause, small bowel intussusceptions are mostly benign. Although surgery is the accepted standard treatment, its necessity in small bowel intussusceptions identified by CT scan is unknown. Twenty-three patients from 2005 to 2008 (16 males; median age, 44 years) with acute abdominal pain and CT-proven small bowel intussusception were studied. Factors associated with the necessity for surgery were determined. Among 11 patients who were managed operatively, surgery was deemed unnecessary in two patients based on negative explorations. Follow up in 10 of 12 patients managed nonoperatively was not associated with any recurrence of intussusception or malignancy (median follow up, 14 months). The only predictor of the need for surgery was CT evidence of small bowel obstruction and/or a radiologically identified lead point, which was present in 7 of 9 (78%) patients having a necessary operation and absent in 12 of 14 (86%) with no indication for surgery (P = 0.008). All small bowel intussusceptions found on CT scan in patients with acute abdominal pain do not require operative management. CT findings of small bowel obstruction and/or presence of a lead point are indications for surgery.