The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Rising incidence of appendiceal neoplasms over time: Does pathological handling of appendectomy specimens play a role?

BACKGROUND: Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. OBJECTIVES: In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. METHODS: Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. CONCLUSION: Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.

A Retrospective Analysis of the Trends in Acute Appendicitis During the COVID-19 Pandemic.

Background: The corona virus disease of 2019 (COVID-19) imposed new public health constraints that deterred people from coming to the hospital. The outcome of patients who developed appendicitis during mandated COVID-19 quarantine has yet to be examined. The main objective was to establish whether there was an increased rate of perforated appendicitis seen during COVID-19 quarantine. Secondary objectives included observing the type of procedure performed, length of stay, and associated complications. Materials and Methods: This retrospective analysis was designed to look at the rates of appendicitis and perforated appendicitis observed during mandatory "safer at home order" from March to May 2020. The same time period a year earlier was used for comparative analysis. The study utilized data gathered from a single health care system, which consisted of a large regional referral center with three emergency rooms (ERs). Patients were included in the study if they presented to any ER in our health care system with a chief complaint of acute appendicitis. Perforated appendicitis was determined either radiographically or intraoperatively. Interventions included surgery, percutaneous drainage, or medical management. Results: There were 107 patients who were included. During quarantine, a total of 48 patients presented with acute appendicitis, with 16 perforations, compared with the previous year where 59 patients presented with acute appendicitis, with 10 perforations (33% versus 17% P = .04). Most patients underwent laparoscopic appendectomy (91%, n = 98), six patients (6%) were managed with intravenous antibiotics and 3 patients (3%) with percutaneous drainage. Patients who perforated had a longer duration of symptoms (2 versus 1, P = .03), white blood cell count (13,190 versus 15,960 cells/mm3, P = .09), and longer operative time (72 versus 89 minutes, P = .01). Patients who perforated had an increased length of stay and rate of complication. Conclusion: There was an overall increased rate of perforated appendicitis seen during quarantine compared with the previous year. Patients with perforated appendicitis had an increased length of stay, longer operative time, and increased rate of complications. Thus, although people were staying home due to public health safety orders, it negatively impacted those who developed appendicitis who may have presented to the hospital otherwise sooner.

Nail Biting as a Cause of Appendicitis.

Ingestion of a foreign body is commonly encountered in clinical practice, but most cause no complications, passing spontaneously through the gastrointestinal tract. However, they can cause obstructive signs and symptoms, and surgical intervention for extraction of the foreign body may be required after identifying its location. We present here the case of a 49-year-old woman who presented to our emergency room with abdominal pain localizing to the right lower quadrant. Evaluation was most consistent with acute appendicitis, and she underwent uncomplicated appendectomy. A keratin nail with Actinomyces was identified in her appendix. Foreign bodies in the appendix can cause simple appendicitis, perforation, periappendiceal abscess, and peritonitis. Regardless of etiology, an appendectomy often ends up the primary treatment, but unusual and rare causes are worth noting if only for the clinician to be aware of when evaluating the next patient with abdominal pain and considering treatment options or future prevention. Our case is an example of a rare scenario in which an Actinomyces-contaminated human nail lodged in the appendix of a woman eventually resulting in acute appendicitis.

Adult Embryonal Sarcoma of the Liver: Management of a Massive Liver Tumor.

Undifferentiated embryonal sarcomas of the liver are extremely rare cases in adults. We report the case of a 30-year-old male who presented with early satiety and abdominal pain due to a massive tumor originating from the left liver and occupying the entire epigastrium. The patient underwent bland embolization in an attempt to decrease the size of the tumor. He then underwent a formal left hepatectomy with resection of liver segments 2, 3, and 4. Extrahepatic inflow control of the portal vein and hepatic artery was performed prior to parenchymal transection. No Pringle maneuver was required. Pathology analysis showed a 45 cm tumor consistent with an undifferentiated embryonal sarcoma and negative microscopic margins. The epidemiology, treatment, and prognosis of this unusual cancer presentation are reviewed.

Laparoscopic Total Gastrectomy with D2 Lymphadenectomy and Side-to-Side Stapled Esophagojejunostomy.

INTRODUCTION: An optimal method has yet to be established for laparoscopic total gastrectomy with intracorporeal anastomosis. METHODS: We aim to describe a simple technique for intracorporeal anastomoses. Technique of laparoscopic total gastrectomy with side-to-side stapled intracorporeal esophagojejunostomy anastomosis and Roux-en-Y jejunojejunostomy is performed on patients with gastric malignancy in an academic community tertiary care center. RESULTS: The anastomotic technique of laparoscopic total gastrectomy with side-to-side stapled esophagojejunostomy is described. CONCLUSION: Laparoscopic total gastrectomy with D2 lymphadenectomy and side-to-side esophagojejunostomy is safe to perform and has the advantage of a wide lumen with low chance for stricture. A laparoscopic total gastrectomy with stapled side-to-side esophagojejunostomy is feasible and safe in advanced gastric cancer.

In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles.

The biological investigation and detection of esophageal cancers could be facilitated with an endoscopic technology to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and investigation through the sensitive and multiplexed detection of cell-surface biomarkers. Here, we demonstrate that the topical application and endoscopic imaging of a multiplexed cocktail of receptor-targeted SERS NPs enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer. Antibody-conjugated SERS NPs were topically applied on the lumenal surface of the rat esophagus to target EGFR and HER2, and a miniature spectral endoscope featuring rotational scanning and axial pull-back was employed to comprehensively image the NPs bound on the lumen of the esophagus. Ratiometric analyses of specific vs. nonspecific binding enabled the visualization of tumor locations and the quantification of biomarker expression in agreement with immunohistochemistry and flow cytometry validation data.

Creation of gastric conduit free-graft with intraoperative perfusion imaging during pancreaticoduodenectomy in a patient post esophagectomy.

As surgery becomes more successful for complicated malignancies, patients survive longer and can unfortunately develop subsequent malignancies. Surgical resection in these settings can be treacherous and manipulations of the patient's anatomy need to be closely considered before embarking on major operations. We report a case of a patient who survived esophageal resection for locally advanced esophageal cancer only to develop a new pancreatic head malignancy. Careful upfront planning allowed for a successful resection with an uncomplicated recovery. She underwent open pancreaticoduodenectomy, and to maintain perfusion to the gastric conduit a microvascular anastomosis of the gastroepiploic pedicle was performed to the middle colic vessels. Intraoperative fluorescent imaging was used to evaluate the anastomosis as well as gastric and duodenal perfusion during the case.

Retrospective comparison of robot-assisted minimally invasive versus open pancreaticoduodenectomy for periampullary neoplasms.

BACKGROUND: As with other open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) may result in decreased pain, fewer wound complications, and accelerated recovery. However, when used for periampullary cancers, it is also important to assess if MIPD offers comparable oncologic outcomes. METHODS: Technical and perioperative outcomes were compared between patients with a preoperative diagnosis of periampullary neoplasm offered MIPD or open pancreaticoduodenectomy (OPD) from November 2009 to July 2011. RESULTS: Fifty-six consecutive MIPD and OPD (28 each) procedures were analyzed. Comparing MIPD to OPD, significant differences included longer median procedure time (431 vs 410 min, p = .04) and fewer median lymph nodes harvested (15 vs. 20, p = .04). R0 resection rate tended to be lower (63 vs. 88%, p = .07) as well as surgical site infections (18 vs. 43 %, p = .08). Clinically significant pancreatic fistula rate was the same between groups (21%). Other outcomes such as narcotic pain medication use, length of stay, and 30-day readmission rates were also similar. CONCLUSIONS: MIPD is feasible with comparable technical success and outcomes to OPD. However, there is a learning curve to the procedure and further experience and prospective study will be required to better establish the oncologic efficacy of MIPD to open resection.

Phase II study of gemcitabine and erlotinib as adjuvant therapy for patients with resected pancreatic cancer.

BACKGROUND: There is currently no consensus about the most effective adjuvant therapy for adenocarcinoma of the pancreas. Both gemcitabine and erlotinib have been demonstrated to improve survival in patients with metastatic disease. This study was designed to evaluate the efficacy of gemcitabine and erlotinib as adjuvant therapy, and to explore potential biomarkers associated with response. METHODS: An institutional review board-approved single-center phase II trial of adjuvant biweekly fixed-dose rate gemcitabine (1500 mg/m(2)) and daily erlotinib (150 mg/day) for 4 months followed by maintenance erlotinib (150 mg/day) over 8 months was initiated. Primary end point was recurrence-free survival (RFS). Epidermal growth factor receptor (EGFR) expression in the resected tumors was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). RESULTS: The study completed planned accrual of 25 patients. Median follow-up was 18.2 (range 11.6-23.5) months. Recurrences were observed in 17 subjects (68%). Median RFS was 14.0 months (95% confidence interval [95% CI], 8.2-24.5) with 1-year and 2-year RFS of 56% (95% CI, 35-73) and 26% (95% CI, 6-52), respectively. Median overall survival was not reached. Estimated 1-year and 2-year overall survival was 84% (95% CI, 63-94) and 53% (95% CI, 22-76), respectively. Nine patients (36%) had a grade 3 event and only 1 (4%) had a grade 4 (neutropenia). Most toxicities were dermatologic, gastrointestinal, and constitutional. There were nonsignificant trends to longer RFS and lower recurrence rates while receiving therapy in subjects with fluorescence in situ hybridization-positive tumors and greater immunohistochemistry expression. CONCLUSIONS: Our phase II results suggest that adjuvant gemcitabine and erlotinib is a promising regimen that merits further investigation.

Short- and long-term costs of laparoscopic colectomy are significantly less than open colectomy.

BACKGROUND: The financial impact of laparoscopic colectomy remains poorly defined. We report the short-term costs of laparoscopic colectomy (LC) as compared with open colectomy (OC) in a high-volume tertiary care hospital, and are the first to incorporate the costs of late, colectomy-related complications in an analysis of long-term costs. METHODS: A retrospective analysis of patients undergoing elective laparoscopic (n = 76) or open (n = 162) colon resection between January 2004 and December 2006 was performed. Primary endpoints were total hospital cost of the index admission and total hospital cost for any subsequent admission for treatment of a colectomy-related complication. RESULTS: Two-hundred thirty-eight patients met inclusion criteria. Mean total hospital cost was significantly greater for patients undergoing OC (US $17,686 per patient versus US $14,518, P = 0.0003). Mean total operative costs were equivalent (US $7,451 OC versus US $7,794 LC, P = 0.274). Average length of stay was shorter for LC (5.2 versus 6.9 days, P < 0.0001). Late complication rates were 5.6% (OC) and 2.6% (LC). Integrating the cost of late complications further increased the disparity between the total cost of OC (US $18,296 per patient, 3.4% increase) as compared with LC (US $14,789, 1.9% increase). CONCLUSION: We demonstrate both short- and long-term financial benefits of LC in a high-volume tertiary care hospital.

Surgical techniques in visceral resection and peritonectomy procedures.

Peritoneal surface malignancies may now be approached with curative intent using a strategy of cytoreductive surgery combined with intraperitoneal chemotherapy. Complete cytoreduction to tumor nodules less than 2.5 mm is considered critical to the efficacy of the local chemotherapy and achieving complete cytoreduction impacts long-term survival. However, this procedure results in significant morbidity with frequent surgical complications. Meticulous technique must be used to limit anastomotic complications, operative time, and blood loss. This review summarizes the major issues surrounding visceral resection and peritonectomy during cytoreductive surgery. Problem areas, which merit special attention, are described, and recommendations are made with regard to surgical technique.

The role of vascular endothelial growth factor in wound healing.

BACKGROUND: A chronic wound is tissue with an impaired ability to heal. This is often a consequence of one of the following etiologies: diabetes, venous reflux, arterial insufficiency sickle cell disease, steroids, and/or pressure. Healing requires granulation tissue depending on epithelialization and angiogenesis. Currently no growth factor is available to treat patients with impaired healing that stimulates both epithelialization and angiogenesis. The objective is to review is the multiple mechanisms of vascular endothelial growth factor (VEGF) in wound healing. MATERIALS AND METHODS: The authors reviewed the literature on the structure and function of VEGF, including its use for therapeutic angiogenesis. Particular attention is given to the specific role of VEGF in the angiogenesis cascade, its relationship to other growth factors and cells in a healing wound. RESULTS: VEGF is released by a variety of cells and stimulates multiple components of the angiogenic cascade. It is up-regulated during the early days of healing, when capillary growth is maximal. Studies have shown the efficacy of VEGF in peripheral and cardiac ischemic vascular disease with minimal adverse effects. Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound. CONCLUSION: VEGF stimulates wound healing through angiogenesis, but likely promotes collagen deposition and epithelialization as well. Further study of the molecule by utilizing the protein itself, or novel forms of delivery such as gene therapy, will increase its therapeutic possibilities to accelerate closure of a chronic wound.

Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinoma.

BACKGROUND: The surgeon's contribution to patients with localized pancreatic adenocarcinoma (PAC) is a margin negative (R0) resection. We hypothesized that a prediction rule based on pre-operative imaging would maximize the R0 resection rate while reducing non-therapeutic intervention. METHODS: The prediction rule was developed using computed tomography (CT) and endoscopic ultrasound (EUS) data from 65 patients with biopsy-proven PAC who underwent attempted resection. The rule classified patients as low or high risk for non-R0 outcome and was validated in 78 subsequent patients. RESULTS: MODEL VARIABLES WERE: any evidence of vascular involvement on CT; EUS stage and EUS size dichotomized at 2.6 cm. In the validation cohort, 77% underwent resection and 58% achieved R0 status. If only patients in the low-risk group underwent surgery, the prediction rule would have increased the resection rate to 92% and the R0 rate to 73%. The R0 rate was 40% higher in low-risk compared with high-risk patients (P < 0.001). High risk was associated with a 67% rate of non-curative surgery (unresectable disease and metastases). CONCLUSION: The prediction rule identified patients most likely to benefit from resection for PAC using pre-operative CT and EUS findings. Model predictions would have increased the R0 rate and reduced non-therapeutic interventions.

Endoscopic ultrasound and computed tomography predictors of pancreatic cancer resectability.

INTRODUCTION: This study investigates the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to predict a margin negative (R0) resection and the need for venous resection in patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients with pancreatic head adenocarcinoma undergoing surgery with intent to resect during the last 5 years were identified. EUS and CT data on vascular involvement were collected. Preoperative imaging was compared to intraoperative findings and final pathology. Contingency table analysis using Fisher's exact test identified imaging features of EUS and CT associated with unresectability and positive margins. RESULTS: Seventy-six patients met study criteria. Forty-seven (62%) underwent potentially curative PD. The R0 resection rate was 70%. There were 16 unresectable patients because of locally advanced disease. Venous involvement>180 degrees and arterial involvement>90 degrees by CT had 100% positive predictive value for failure to achieve R0 resection (p<.01). If patients with prestudy biliary stents were excluded, EUS venous abutment or invasion also predicted R0 failure (p=.02). Combined but not individual EUS and CT findings were predictive of need for vein resection. CONCLUSIONS: Pancreas protocol CT imaging appears to be a better predictor of resectability compared to EUS. EUS accuracy is affected by the presence of biliary stents.

Laparoscopic surface scanning and subsurface targeting: implications for image-guided laparoscopic liver surgery.

Segmental liver resection and locoregional ablative therapies are dependent upon accurate tumor localization to ensure safety as well as acceptable oncologic results. Because of the liver's limited external landmarks and complex internal anatomy, such tumor localization poses a technical challenge. Image guided therapies (IGT) address this problem by mapping the real-time, intraoperative position of surgical instruments onto preoperative tomographic imaging through a process called registration. Accuracy is critical to IGT and is a function of: 1) the registration technique, 2) the tissue characteristics, and 3) imaging techniques. The purpose of this study is to validate a novel method of registration using an endoscopic Laser Range Scanner (eLRS) and demonstrate its applicability to laparoscopic liver surgery. Six radiopaque targets were inserted into an ex-vivo bovine liver and a computed tomography (CT) scan was obtained. Using the eLRS, the liver surface was scanned and a surface-based registration was constructed to predict the position of the intraparenchymal targets. The target registration error (TRE) achieved using our surface-based registration was 2.4 +/- 1.0 mm. A comparable TRE using traditional fiducial-based registration was 2.6 +/- 1.7 mm. Compared to traditional fiducial-based registration, laparoscopic surface scanning is able to predict the location of intraparenchymal liver targets with similar accuracy and rate of data acquisition.

Development of a three-dimensional freehand endorectal ultrasound system for use in rectal cancer imaging.

The initial study reporting the accuracy of an optically tracked endorectal ultrasound (TERUS) probe for the purpose of improving the staging of rectal cancer is presented here. In this work we describe the need for a more accurate ERUS system and why the incorporation of image guidance makes this goal feasible. A rectal phantom was constructed with five targets placed in positions where tumors normally occur. The locations of these targets were found using two different imaging modalities, CT and ultrasound, and the target registration error (TRE) between these two image sets was calculated. The average TRE of 33 image captures of the five targets using TERUS was 2.1 mm. This is a promising outcome because the desired tumor margins for rectal cancer are on the order of centimeters. These preliminary results support the proof of concept for a TERUS system that should improve ultrasound imaging in rectal cancer.

Resection of mesenteric inflammatory veno-occlusive disease causing ischemic colitis.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of mesenteric ischemia that is diagnosed by histologic examination of the operative specimen. Recurrence of symptoms occurs, but further resection of ischemic intestine is seldom required. We describe the case of MIVOD in a young patient with clinical findings of ischemic colitis. The patient experienced complete resolution of the process, thus confirming the relatively benign course of this disease following resection. This report substantiates resolution of the inflammatory process after resection, colostomy, and reanastomosis. We review the literature and make conclusions regarding the clinical management of this disease.