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Operations for esophageal and proximal gastric cancers are increasing. The most common surgical intervention performed for this patient population is esophagectomy. Regardless of the technical approach pursued, creation of a neo-esophageal conduit imposes various anatomic and physiologic challenges. These patients often undergo additional endoscopic and surgical revision procedures to improve their quality of life. Some of the most common complications encountered by medical professionals managing these challenging patients include para-conduit hiatal hernias, acid and biliary reflux, and redundant or dysfunctional neo-esophageal conduit. As survival and long-term outcomes improve, clinicians are encountering novel complications including conduit neoplasia and tracheal conduit fistulas. This review highlights some of the common complications post esophagectomy with focus on initial diagnosis and management strategies.

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the

Intraoperative molecular imaging (IMI)-guided resections have been shown to improve oncologic outcomes for patients undergoing surgery for solid malignancies. The technology utilizes fluorescent tracers targeting cancer cells without the use of any ionizing radiation. However, currently available targeted IMI tracers are effective only for tumors with a highly specific receptor expression profile, and there is an unmet need for IMI tracers to label a broader range of tumor types. Here, we describe the development and testing of a novel tracer (CR)-S0456) targeted to the sodium multivitamin transporter (SMVT).Preclinical models of fibrosarcoma (HT-1080), lung (A549), breast (4T1), and renal cancers (HEK-293 T) in vitro and in vivo were used for assessment of (CR)-S0456 specific tumor labeling via sodium-mediated SMVT uptake in dipotassium phosphate or choline chloride-containing media buffer. Additionally, pharmacologic inhibition of multiple intracellular coenzyme-R obligate signaling pathways, including holocarboxylase synthetase (sulconazole nitrate), PI3K/AKT/mTOR (omipalisib), and calmodulin-dependent phosphatase (calmidazolium), were investigated to assess (CR)-S0456 uptake kinetics. Human fibrosarcoma-bearing xenografts in athymic nude mice were used for tumor and metabolic-specific labeling. Novel NIR needle confocal laser endomicroscopic (nCLE) intratumoral sampling was performed to demonstrate single-cell specific labeling by CR-S0456.CR-S0456 localization in vitro correlated with highly proliferative cell lines (MTT) and doubling time (p 0.05) with the highest microscopic fluorescence detected in aggressive human fibrosarcomas (HT-1080). Coenzyme-R-specific localization was demonstrated to be SMVT-specific after competitive inhibition of internal localization with excess administration of pantothenic acid. Inhibiting the activity of SMVT by affecting sodium ion hemostasis prevented the complete uptake of CR-S0456. In vivo validation demonstrated (CR)-S0456 localization to xenograft models with accurate identification of primary tumors as well as margin assessment down to 1 mmThese findings suggest that a SMVT-targeted NIR contrast agent can be a suitable tracer for imaging a wide range of malignancies as well as evaluating metabolic response to systemic therapies, similar to PET imaging with immune checkpoint inhibitors.

BACKGROUND: Intraoperative molecular imaging (IMI) has been shown to improve lesion detection during pulmonary sarcomatous metastasectomy. Our goal in this study was to evaluate whether data garnered from IMI-guided resection of pulmonary sarcoma metastasis translate to improved patient outcomes. STUDY DESIGN: Fifty-two of 65 consecutive patients with a previous history of sarcomas found to have pulmonary nodules during screening were enrolled in a nonrandomized clinical trial. Patients underwent TumorGlow the day before surgery. Data on patient demographics, tumor biologic characteristics, preoperative assessment, and survival were included in the study analysis and compared with institutional historical data of patients who underwent metastasectomy without IMI. p values < 0.05 were considered significant. RESULTS: IMI detected 42 additional lesions in 31 patients (59%) compared with the non-IMI cohort where 25% percent of patients had additional lesions detected using tactile and visual feedback only (p < 0.05). Median progression-free survival (PFS) for patients with IMI-guided pulmonary sarcoma metastasectomy was 36 months vs 28.6 months in the historical cohort (p < 0.05). IMI-guided pulmonary sarcoma metastasectomy had recurrence in the lung with a median time of 18 months compared with non-IMI group at 13 months (p < 0.05). Patients with synchronous lesions in the IMI group underwent systemic therapy at a statistically higher rate and tended to undergo routine screening at shorter interval. CONCLUSIONS: IMI identifies a subset of sarcoma patients during pulmonary metastasectomy who have aggressive disease and informs the medical oncologist to pursue more aggressive systemic therapy. In this setting, IMI can serve both as a diagnostic and prognostic tool without conferring additional risk to the patient.

Located in the mediastinum, pericardial cysts are rare and benign congenital abnormalities commonly identified as incidental findings on imaging. However, some patients with abnormally enlarged cysts present with compressive symptoms, which include recurrent infections, tamponade from cardiac compression and respiratory complications. Our report highlights a challenging case of a patient with recurrent respiratory symptoms secondary to phrenic nerve compression. Misdiagnosis over the past decade resulted in ineffective interventions. After clear identification of the cyst compression of the ipsilateral phrenic nerve, the patient underwent a minimally invasive robotically assisted cyst resection with phrenic nerve preservation that alleviated respiratory symptoms.

Background Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. Methods Patients with American Joint Committee on Cancer (8th edition) stage I–IV MCC treated at our institution were identified (1/1/2008–2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. Results Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20–66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). Conclusions Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

Intraoperative molecular imaging (IMI) with folate-targeted NIR tracers has been shown to improve lesion localization in more than 80% of lung adenocarcinomas. However, mucinous adenocarcinomas (MAs) and invasive mucinous adenocarcinomas (IMAs) of the lung, which are variants of adenocarcinoma, appear to have decreased fluorescence despite appropriate folate receptor expression on the tumor surface. We hypothesized that the etiology may be related to light excitation and emission through non-Newtonian fluid (mucin) produced by goblet and columnar cancer cells.Intraoperative data for 311 subjects were retrospectively reviewed from a prospectively collected 6-year database. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (pafolacianine, folate receptor-targeted NIR fluorochrome) for lung cancer resections. Then, the ratio of the mean fluorescence intensity of the tumors and background tissues (TBR) was calculated. Tumors were examined for mucin, FRa, FRb, and immunofluorescent tracer uptake by a board-certified pathologist. The optical properties of mucin analyzed by imaging software were used to create in vitro gel models to explore the effects on NIR tracer fluorescence intensity.A large proportion (192, 62%) of the patients were female, with an average of 62.8 years and a 34-year mean pack smoking history. There were no severe (Clavien-Dindo gt; III) complications related to pafolacianine infusion. A total of 195 lesions in the study were adenocarcinomas, of which 19 (6.1%) were of the mucinous subtype. A total of 14/19 of the patients had a smoking history, and more than 74% of the IMA lesions were in the lower lobes. IMA lesions had a lower in situ TBR than nonmucinous adenocarcinomas (2.64 SD 0.23) vs (3.45 SD 0.11), respectively (p lt; 0.05). Only 9/19 (47%) were localized in situ. Tumor bisection and removal of mucin from IMAs significantly increased pafolacianine fluorescence, with resultant TBR not being significantly different from the control group (4.67 vs 4.89) (p = 0.19). Of the 16 lesions that underwent FR expression analysis, 15/16 had FR presence on cancer cells or tumor-associated macrophages in the tumor microenvironment. There was no statistically significant difference in fluorescence intensity during immunofluorescence analysis (4.99 vs 5.08) (p = 0.16). Physical removal of mucin from IMAs improved the TBR from 3.11 to 4.67 (p lt; 0.05). In vitro analysis of the impact of synthetic non-Newtonian fluid (agarose 0.5%) on NIR tracer fluorescence showed a decrease in MFI by a factor of 0.25 regardless of the concentration for each 5 mm thickness of mucin.The mucinous subtype of lung adenocarcinomas presents a unique challenge in pafolacianine-targeted IMI-guided resections. The presence of non-Newtonian fluids presents a physical barrier that dampens the excitation of the tracer and fluorescence emission detected by the camera. Knowledge of this phenomenon can allow the surgeon to critically analyze lesion fluorescence parameters during IMI-guided lung cancer resections.

Intraoperative molecular imaging has emerged as a potential tool in addressing challenges faced during lung cancer surgery by localizing small lesions, ensuring negative margins, and identifying synchronous cancers. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) glycoprotein has emerged as a potential target in fluorescent labeling of non-small cell lung cancer given the high antigen density in tumor cells and absence of expression in normal parenchyma. The goal of our study was to determine whether anti-CEACAM5 targeted near-infrared fluorochrome could be a suitable target in non-small cell lung cancer.The CEACAM5 expression was evaluated in AB-12 (known negative control), HT29 (known positive control), and H460 (non-small cell lung cancer) cell lines by polymerase chain reaction. SGM-101, a CEACAM5 antibody, coupled with a BM-104 near-infrared fluorescent tracer was evaluated with dose escalation, in vitro cellular localization, and immunofluorescence microscopy. Subsequently, in vivo validation was performed in 52 athymic nude xenografts.Polymerase chain reaction analysis demonstrated 3000x relative expression of CEACAM5 in HT-29 cells compared with AB-12. The H460 cells showed 1000x relative expression compared with AB12 (P.05). Both HT29 and H460 cells showed tracer internalization with signal to background ratio of 4.5 (SD 0.34) whereas there was minimal uptake by AB12 cells with signal to background ratio 1.1 (SD 0.1; P.05). There was linear fluorescence increase with increasing tracer dosing in receptor expressing cell lines. In preclinical models, HT-29 and H460 cells lines produced near-infrared fluorescence with average tumor to background ratio of 3.89 (SD 0.25) irrespective of tumor size compared with no fluorescence by AB12 tumors (P.05). The CEACAM5 expressing tumors had excellent dye uptake compared with AB12 tumors.CEACAM5 serves as a possible receptor for targeted intraoperative molecular imaging resections in lung cancer. This study sets a path for evaluation of CEACAM5 targets in future clinical trials.

ImportanceLocalization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor.ObjectiveTo evaluate the suitability of SGM-101, a carcinoembryonic antigen–related cell adhesion molecule type 5 (CEACAM5) receptor–targeted near-infrared fluorochrome, for molecular imaging–guided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas.Design, Setting, and ParticipantsFor this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study.InterventionsSGM-101 (10 mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope.Main Outcomes and MeasuresSGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence.ResultsTen patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining.Conclusions and RelevanceThis in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials.Trial RegistrationClinicalTrials.gov identifier: NCT04315467

One of the novel advancements to enhance the visual aspects of lung cancer identification is intraoperative molecular imaging (IMI), which can reliably detect tumors that would otherwise be missed by standard techniques such as tactile and visual feedback, particularly for sub-centimeter or ground-glass nodules. However, there remains a subset of patients who do not benefit from IMI due to excessive background fluorescence secondary to parenchymal light-absorbing carbon deposition. Our goal was to identify the effects of these carbonaceous materials on the quality of IMI-guided lung cancer resections.Between July 2014 and May 2021, a total of 311 patients were included in the study. Patients underwent infusion of the study drug OTL38 or ICG up to 24 h prior to VATS for lung cancer. Several factors such as age, tumor subtype, PET SUV, smoking, demographics, chronic lung conditions, patient domicile, and anthracosis were analyzed with respect to lung fluorescence during IMI. P values 0.05 were considered statistically significant.Variables such as age, sex, and race had no statistical correlation to IMI success. However, smoking status and pack year had a statistically significant correlation with background parenchymal fluorescence and lung inflammation (p 0.05). MFI of background (lung parenchyma) correlated with smoking history (p 0.05) which led to decreased tumor-to-background ratio (TBR) measurements for all patients with proven malignancy (p 0.05). Patients with chronic lung disease appear to have increased background parenchymal fluorescence regardless of smoking history (287 vs. 154, p 0.01). City dwellers compared to other groups appear to be exposed to higher pollutant load and have higher rates of anthracosis, but living location's impact on fluorescence quantification appears to be not statistically significant.Smokers with greater than 10 PPY and those with chronic lung disease appear to have decreased lesion-to-background discrimination, significant anthracosis, and reduced IMI efficacy secondary to light-absorbing carbon deposition.

Soft-tissue sarcomas (STS) are a group of lethal mesenchymal tumors that are a major cause of cancer related morbidity for those under the age of 20.PI3K inhibitors have been found to be effective against subset of STS but are associated with significant toxicities limiting their use.We have thought to test a selective fibroblast activation protein (FAP) targeted delivery of PI3K/AKT/mTOR inhibitor omipalisib to STS in pre-clinical setting as FAP is overwhelmingly expressed agressive soft tissue malignancies. Experimental Design: Patient derived fibrosarcomas (aSMA-,FAP+,pAKT+) were isolated by flow cytometry.FAP(-)HT1080 fibrosarcoma cell lines were used as a negative control whereas methylcoanthrene induced mouse fibrosarcoma transfected with human FAP cDNA were used as positive control.Cell expression of FAP,AKT,mTOR was compared using SDS Page,IHC,and flow cytometry.FAP ligand coupled to omipalisib(FAPL-PI3Ki)was then evaluated in-vitro and in small animal models. Results: Cell lines with known FAP expression demonstrated significant uptake of FAPL conjugated NIR fluorochrome.Wild type cells(hFAP-) showed no ligand binding both in flow cytometry and fluorescent microscopy(p Citation Format: Feredun Azari, Gregory T. Kennedy, Ashley Chang, Bilal Nadeem, Azra Din, Isvita Marfatia, Steven Albelda, Philip Low, Madduri Srinivasarao, Ramesh Mukkamala, Neil T. Sullivan, Evgeniy Eruslanov, Sunil Singhal. Selective delivery of fibroblast activation protein conjugated dual phosphoinositide 3-kinase–AKT Kinase-mTOR inhibitor associated with decreased tumor proliferation and on-target toxicity in high-grade soft-tissue sarcomas [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A016.

BACKGROUND: Pulmonary ground glass opacities (GGOs) are early-stage adenocarcinoma spectrum lesions that are not easily palpable. Challenges in localizing GGOs during intraoperative pathology can lead to imprecise diagnoses and additional time under anesthesia. To improve localization of GGOs during frozen section diagnosis, we evaluated a novel technique, 3-dimensional near-infrared specimen mapping (3D-NSM). METHODS: Fifty-five patients with a cT1 GGO were enrolled and received a fluorescent tracer preoperatively. After resection, specimens were inspected to identify lesions. Palpable and nonpalpable nodules underwent 3D-NSM and the area of highest fluorescence was marked with a suture. Time for 3D-NSM, time for frozen section diagnosis, and number of tissue sections examined were recorded. To compare 3D-NSM with standard-of-care techniques, a control cohort of 20 subjects with identical inclusion criteria were enrolled. Specimens did not undergo 3D-NSM and were sent directly to pathology. RESULTS: 3D-NSM localized 54 of 55 lesions with 1 false negative. All 41 palpable lesions were identified by 3D-NSM. Thirteen (92.8%) of 14 nonpalpable lesions were located by 3D-NSM. Time to diagnosis for the 3D-NSM cohort was 23.5 minutes, compared with 26.0 minutes in the control cohort (P = .04). 3D-NSM did not affect time to diagnosis of palpable lesions (23.2 minutes vs 21.4 minutes; P = .10). 3D-NSM significantly reduced time to diagnosis for nonpalpable lesions (23.3 minutes vs 34.4 minutes; P < .0001). 3D-NSM also reduced the number of tissue sections analyzed in nonpalpable lesions (4.50 vs 11.00; P < .0001). CONCLUSIONS: 3D-NSM accurately localizes GGOs and expedites intraoperative diagnosis by reducing the number of tissue sections analyzed for nonpalpable GGOs.

Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescenttargeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials.Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties.Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's second clinical trials update on IMI were selected to discuss their clinical trials and endpoints.Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures.Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

OBJECTIVES Although initial portal vein reperfusion of a liver allograft is nearly standardized, limited data suggest initial hepatic artery reperfusion may improve hemodynamics and posttransplant outcomes. MATERIALS AND METHODS We retrospectively reviewed orthotopic liver transplants performed between January 2013 and February 2018. Parameters of liver recipients with initial hepatic artery reperfusion were compared with those with initial portal vein reperfusion. RESULTS Of 204 recipients, 53 (26%) were initially perfused from the hepatic artery and 151 (74%) were initially perfused from the portal vein. Demographics between groups did not differ. There were no significant differences in the incidence of acute rejection between recipients with initial hepatic artery reperfusion versus portal vein reperfusion at 3 months and 1 year (1.9% vs 7.9% and 7.5% vs 10.6%; not significant), hepatic artery thrombosis (1.9% vs 4.0% and 1.9% vs 7.3%; not significant), biliary leakage (7.5% vs 4.0% and 9.4 vs 6.6; not significant), biliary strictures (7.5% vs 5.3% and 11.3% vs 7.9%; not significant), or portal or hepatic venous thrombosis/stenosis (5.7% vs 5.3% and 7.5% vs 7.9%; not significant). Furthermore, recipients with initial hepatic artery reperfusion and portal vein reperfusion were both hospitalized for a median of 8.5 days (interquartile range, 6.5-15.5 vs 7.0-14.0 days, respectively), and both groups were in the intensive care unit for a median of 3 days (interquartile range, 2-7 vs 2-4 days, respectively). Initial hepatic artery reperfusion was associated with significantly less intraoperative packet red blood cell transfusion (median, 11.9 U [interquartile range, 11.1-13.1 U] vs 15.5 U [interquartile range, 12.9-17.9 U]; P < .001). The 2 groups did not differ in terms of patient and graft survival. CONCLUSIONS Initial reperfusion of liver allografts with arterial, rather than portal, blood has benefits to hemodynamic stability, did not have deleterious effects on outcomes, and resulted in less intraoperative blood utilization.

INTRODUCTION: Cancer surgery has multiple challenges including localizing small lesions, ensuring negative margins, and identifying synchronous cancers. One of the tools proposed to address these issues is intraoperative molecular imaging (IMI). An important consideration in IMI is the quantification of the tumor fluorescence during the procedure and using that data to add clinical value. Currently, the most commonly cited measure of quantification is the tumor-to-background ratio (TBR). Our goal was to evaluate the clinical value of TBR measured with OTL38 NIR tracer during a lung cancer resection. METHODS: Intraoperative data was retrospectively reviewed from a prospectively collected 5-year database. Between 2015 and 2020, 279 patients were included in the study. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (OTL38) for lung cancer resections, then, the Mean Fluorescence Intensity of the tumors and background tissues were calculated. To evaluate the clinical efficacy of the TBR calculation, the results were correlated with patient, biologic, tumor, and technological factors. RESULTS: For pulmonary surgery, patient factors such as gender, age, smoking history, and time from infusion of OTL38 to surgery did not have any statistical significance in predicting the TBR during surgery. In addition, TBR measurements did not correlate with location of the tumor in the lung (p=0.123). There was no statistical correlation of preoperative positron emission tomography measurements [standardized uptake value] with intraoperative TBR. However, there was statistically significant negative correlation of in-situ TBR measurement and the distance of the lesion from the surface of the organ (p

Background Xanthogranulomatous cholecystitis is a particularly destructive variant of cholecystitis marked by unique inflammatory changes evident in pathologic specimens. Multiple case series have evaluated this process. However, these often focus on differentiating it from malignancy and have largely been conducted in Asia, where the disease may differ from that seen in the Western hemisphere. This study evaluated surgical outcomes after cholecystectomy for xanthogranulomatous cholecystitis at a high-volume tertiary care institution in the United States. The goal was to determine whether the process can be identified preoperatively and whether modifications should be made to the operative approach in this setting. Methods Patients with histopathological confirmation of xanthogranulomatous cholecystitis who underwent cholecystectomy between 2002 and 2019 were identified from an updated institutional database. Data regarding demographics, imaging findings, surgical procedures, and perioperative complications were reviewed retrospectively. A cohort of patients undergoing cholecystectomy for more typical diagnoses was also identified for comparison. Results Twenty-seven patients with a histopathologic diagnosis of xanthogranulomatous cholecystitis were identified. The median age was 64, and 17/27 (63.0%) were male. The majority of cases were done electively on patients admitted that day (17/27). Seventeen patients were evaluated with diagnostic ultrasonography, 21 with computed tomography scan, and 8 with magnetic resonance imaging; 21/27 patients had multiple modality studies. The most common singular finding was gallbladder wall thickening, but the radiographic findings were otherwise inconsistent. Twenty-five patients had planned laparoscopic cholecystectomies, but only 10 were completed. Only 8 of the 15 converted procedures were completed as simple cholecystectomies. Five patients required subtotal cholecystectomy. Median estimated blood loss was 250 cm3, and the median time of procedure was nearly 3 hours. Eight patients had complications, including 6 severe complications such as intraoperative bile duct injury. Conclusion Xanthogranulomatous cholecystitis unfortunately has a nonspecific presentation, which can make it difficult to recognize preoperatively. It is to be suspected in cases featuring a distended, severely inflamed gallbladder that does not match the benign appearance of the patient. When the diagnosis is suspected, an open approach is justified and patients should be counseled as to the increased likelihood of atypical approaches and elevated risk of complication. Referral to a hepatobiliary specialist is to be considered.

Initially reported by Hattori et al. in 2005, there have been recent reports of posterior mediastinal cysts with developmental endosalpingiosis-mullerianosis, also known as Mullerian cysts. Here, we present a unique case of symptomatic posterior mediastinal Mullerian cyst in a 47-year-old female managed with robotic-assisted thoracoscopic surgery. The final diagnosis was confirmed with the histopathologic assessment, which showed the lesion was positive for estrogen, progesterone, PAX8, and WT1 receptors. Mullerian cysts of the posterior mediastinum can cause compressive effects on nearby stellate ganglion, causing symptoms suggestive of the sympathetic storm. These cysts should be evaluated by a dedicated thoracic and gynecologic pathologist for accurate diagnosis. Thoracic surgeons and Gynaecologists should consider these lesions in patients with appropriate clinical and demographic characteristics.

Objective: Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and affect neoplastic progression by stromal remodeling, paracrine signaling, potentiating cancer cell proliferation, and immune system evasion. As such, they are a potential target for optimizing therapeutic and diagnostic strategies. The purpose of our study was to evaluate if Fibroblast Activation Protein (FAP) can be a suitable target for molecular imaging guided cancer localization during surgery because FAP is overwhelmingly expressed by CAFs. Methods: Patient derived lung adenocarcinoma FAP+/alpha SMA+ myofibroblasts (CAFs) were isolated by flow cytometry and cultured according to institutional best practices. Normal fibroblasts from 3T3 cell line were used as negative control whereas normal lung fibroblasts transfected with human FAP cDNA were used as positive control. Cell expression of FAP was compared using SDS Page analysis and flow cytometry. FAP ligand coupled to NIR S0456 fluorochrome (FAP-S0456) was then evaluated with in-vitro dose escalation, cell-toxicity study, fluorescence parameters, and immunofluorescence microscopy. Results: Patient derived lung cancer (LC) CAFs had lower FAP-S0456 dye binding expression compared to transfected fibroblasts (TF), while normal fibroblasts (FAP-, aSMA-) had no FAP-S0456 dye binding detected on FACS direct antibody analysis (MFI 1033 vs 244, p Conclusion: FAP transmembrane receptor is highly expressed in cancer associated fibroblasts and can serve as a potential target for FAP ligand conjugated near-infrared tracers. This study demonstrates proof of principle of utilizing FAP-S0456 in CAF in-vitro models and paves a path for pre-clinical diagnostic and therapeutic validation for surgical applications. Citation Format: Feredun Azari, Gregory Kennedy, Ashley Chang, Bilal Nadeem, Neil Sullivan, Emanuel Encarnado, Steven Albelda, Evgeniy Eruslanov, Sunil Singhal. Fibroblast activation protein transmembrane receptor targeted near-infrared fluorochrome specifically identifies patient derived lung cancer associated fibroblasts in pre-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4142.

Lung cancer is the most frequent cause of cancer-related death worldwide. Despite advances in systemic therapy, the 5-year survival remains humbling at 4% to 17%. For those diagnosed early, surgical therapy can yield potentially curative results. Surgical resection remains a cornerstone of medical care. Success hinges on sound oncologic resection principles. Various techniques can be used to identify pulmonary nodules. A challenge is intraoperative assessment of the surgical specimen to confirm disease localization and ensure an R0 resection. The primary tool is frozen section. Understanding the options available enhances the arsenal of thoracic surgeons and leads to better patient care.

Background Periampullary malignancies are often unresectable tumors that frequently cause biliary or duodenal obstruction. Advances in endoscopic and percutaneous options have lessened the need for operative palliation. Nevertheless, many patients are still found to be unresectable at the time of exploration, making palliative bypass a consideration. Several prior studies have examined the morbidity of operative palliation, but many were conducted over lengthy time periods, and few have examined the impact of these procedures on future therapy. This study is a contemporary analysis of the short- and long-term outcomes of palliative bypass procedures for unresectable periampullary malignancies at a single high-volume institution. Methods We identified a contemporary cohort of patients in whom a pancreatoduodenectomy was planned for periampullary malignancy but instead underwent an aborted procedure. Patients were divided into 5 procedure groups: laparoscopy only, laparotomy with or without cholecystectomy, gastrointestinal bypass, biliary bypass, and double bypass (gastrointestinal and biliary). Data regarding the patient cohort, procedures, morbidity/mortality, and the interval to initiation of systemic therapy were collected prospectively and reviewed retrospectively. Results Between July 2011 and November 2018, 128 out of 615 (17%) patients had an aborted pancreatoduodenectomy; 113 out of 128 patients had pancreatic adenocarcinoma, and 86 (67.1%) had duodenal or biliary obstruction at the time of operation. Patients who underwent laparoscopy only (n = 34) had no operative complications and a 90-day mortality of 6%; 88% of these patients went on to receive systemic therapy (median 21 days postprocedure). Double bypass was associated with a far lesser complication rate than in prior studies; 17% of patients had some complication(s), but only 9% had a severe complication. The 90-day all-cause mortality was 13%, and only 71% of these patients went on to receive systemic therapy (median 47 days postprocedure). Notably, 27 out of 34 (79%) of patients who underwent laparoscopy alone needed additional procedures for local obstruction, whereas only 5 out of 42 (12%) double bypass patients needed additional interventions. Median survival for the entire cohort was 10.3 months. Conclusion Palliative procedures in this cohort had a far lesser complication rate than that of historical series. Palliative procedures, however, delayed systemic therapy, and a fair number of patients never received additional treatments. Palliative procedures markedly decreased the need for future interventions. Intraoperative decisions regarding palliative procedures must incorporate the functional status and motivations of the patient; these procedures are increasingly safe but may still affect survival.

Highlights • Transplanted pancreas venous thrombosis is a complex to diagnose. • Urgent and prompt treatment is necessary. • Endovascular pharmacomechanical thrombectomy sometimes possible. • Early intervention can salvage graft organs in those receiving simultaneous pancreas and kidney transplantation., Introduction Simultaneous kidney and pancreas transplant is the preferred treatment option for end-stage renal disease due to type 1 diabetic nephropathy. Vascular complications are detrimental to graft survival and can lead to graft loss in the early postoperative phase of transplantation. Generally, duplex Doppler ultrasound is used for vascular patency monitoring and pancreatectomy followed by re-transplantation is required in the majority of cases. Recently, pancreatic graft salvage with non-operative management, including medical anticoagulation and endovascular thrombectomy, in the early postoperative period has been described with success. Presentation of case We report a case of early detection of pancreas venous graft thrombosis via clinical suspicion and radiological methods, and early intervention with endovascular thrombolysis. As a result, the pancreatic graft was successfully salvaged. Discussion A limited number of studies had showed successful graft salvage in only 30–45% of thrombosed pancreatic graft with surgical thrombectomy. Our patient also had bleeding from the vascular access site and ultimately required blood transfusion, however she recovered well after procedure. Conclusion Given the complexity and significance of PVGT, urgent and prompt treatment is necessary. Interpreting outcomes from our case and other small studies, it appears that endovascular pharmacomechanical thrombectomy can be a vital tool to salvage graft organs in those receiving SPK.

Importance Complete (R0) resection is the dominant prognostic factor for survival across solid tumor types. Achieving adequate tumor clearance with appropriate margins is particularly difficult in nonpalpable tumors or in situ disease. Previous methods to address this problem have proven time consumptive, impractical, or ineffective. Objective To assess the capability of intraoperative molecular imaging (IMI), a novel technology using a fluorescent tracer targeted to malignant cells, to localize visually occult, nonpalpable tumors and quantify margin distances during resection. Design, setting, and participants This nonrandomized open-label trial of IMI using a folate receptor-targeted fluorescent tracer enrolled patients between May 2017 and June 2020 at a single referral center. Eligible patients included those with a small (T1) lung lesion suspicious for malignant neoplasms and with radiographic features suggestive of a nonpalpable lesion. Interventions Patients were preoperatively infused with a folate receptor-targeted near-infrared tracer. Intraoperatively, surgeons used thoracoscopic visualization and palpation to identify lesions. IMI was performed to detect the lesion in situ, and lesions were imaged ex vivo. Margins were assessed by IMI before comparison with those reported on final histopathologic analysis. Main outcomes and measures The main outcomes were whether IMI could (1) localize nonpalpable lung lesions in situ and (2) quantify margin distance with comparison with final pathology as the criterion standard. Patient demographic information and lesion characteristics were prospectively recorded. Results Of 40 patients, 26 (65%) were female, and the median (interquartile range) age was 66.5 (62-72) years. Conventional surgical methods localized 22 of 40 lesions (55%), while IMI localized 36 of 40 (90%). Of 18 nonpalpable lesions, 15 (83.3%) were identified by IMI. Both palpable and nonpalpable lesions demonstrated mean signal-to-background ratio more than 2. An IMI margin was able to be calculated for 39 of 40 patients (95%). IMI margins were nearly identical to margins reported on final pathology (R2 = 0.9593), with median (interquartile range) difference of 1.3 (0.7-2.0) mm. IMI detected 2 margins in nonpalpable tumors that were clinically unacceptable and would have had a high probability of recurrence. Conclusions and relevance To our knowledge, this study presents the first clinical use of IMI for nonpalpable tumors and provides proof of principle for the utility of IMI across the field of surgical oncology in identifying occult disease and tumor-positive margins.

OBJECTIVES Despite the present use ofthe laparoscopic technique for living-donor kidney nephrectomy, a search for alternative techniques continues.The aim of this study was to compare finger-assisted open donor nephrectomy versus laparoscopic donor nephrectomy. MATERIALS AND METHODS This study included retrospective data of 95 consecutive donors in a transplant center who were under going donor nephrectomy RESULTS: Donor demographics and clinical characteristics were generally similar between treatment groups. There were fewer female donors in the finger-assisted open donor nephrectomy treatment group (70.5% vs 29.5%; P = .003), but median body mass index was similar between groups (28 vs 26 kg/m²; P = .032). Patients who received laparoscopic donor nephrectomy had longer operative duration (3.5 vs 1.2 h; P < .001), longer combined length of incision (6 vs 5 cm; P = .001), andshorter median hospital length of stay (3 vs 4 days; P < .001). A left nephrectomy was preferred in both groups. Minor postoperative complications occurred less often in the finger-assisted open donor nephrectomy group (14.7% vs 31.6%; P = .0094). Donors who received laparoscopic nephrectomy had lower glomerular filtration rate at 1 year after donation (60 vs 89 mL/min/1.73 m²; P < .001) than donors who received finger-assisted nephrectomy. However, recipients of donors of both procedures had similar glomerular filtration rate at 1 year after transplant (65 vs 69 mL/min/1.73 m²; P = .5). CONCLUSIONS Our study demonstrated that finger-assisted open donor nephrectomy is a successful and safe alternative versus laparoscopic donor nephrectomy, providing favorable results for patients in terms of complications and outcomes.

Sentinel lymph node biopsy (SLNB) has been somewhat controversial for patients with a diagnosis of thick (> 4 mm) melanoma. This study aimed to characterize the national practice pattern in performing SLNB for this patient population and to determine the predictors and prognostic value of nodal positivity using population-level data. Patients with a diagnosis of clinically node-negative, thick melanoma (2010–2015) were identified using the National Cancer Database. Factors associated with performing regional nodal evaluation were characterized. Predictors of nodal positivity were determined using multivariable logistic regression. Overall survival (OS) was estimated using standard statistical methods. Of 9847 study patients, 7513 (76.3%) underwent SLNB. The patients who underwent nodal evaluation were younger (median age, 66 vs 81 years; P

Esophageal and gastric carcinomas are prevalent malignancies worldwide. In contrast to the poor prognosis associated with advanced stages of disease, early stage disease has a favorable prognosis. Early stage gastric cancer (ESGC) is defined as cancer in which the depth of invasion is limited to the submucosal layer of the stomach on histologic examination, regardless of lymph node status. ESGC that meets standard or expanded criteria can be treated via endoscopic mucosal resection and endoscopic submucosal dissection. Similar indications for endoscopic interventions exist for gastroesophageal junction and esophageal malignancies."

This paper introduces a Spatial Vector Autoregressive Moving Average (SVARMA) model in which multiple cross-sectional time series are modeled as multivariate, possibly fat-tailed, spatial autoregressive ARMA processes. The estimation requires specifying the cross-sectional spillover channels through spatial weights matrices. the paper explores a kernel method to estimate the network topology based on similarities in the data. It discusses the model and estimation, focusing on a penalized Maximum Likelihood criterion. The empirical performance of the estimator is explored in a simulation study. The model is used to study a spatial time series of pollution and household expenditure data in Indonesia. The analysis finds that the new model improves in terms of implied density, and better neutralizes residual correlations than the VARMA, using fewer parameters. The results suggest that growth in household expenditures precedes pollution reduction, particularly after the expenditures of poorer households increase; that increasing pollution is followed by reduced growth in expenditures, particularly reducing the growth of poorer households; and that there are significant spillovers from bottom-up growth in expenditures. The paper does not find evidence for top-down growth spillovers. Feedback between the identified mechanisms may contribute to pollution-poverty traps and the results imply that pollution damages are economically significant.

Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.

Concomitant septic arthritis in the presence of crystalline disease is a rare presentation of acute hemarthrosis and knee pain. Literature review showed that co-occurrence of these entities is an infrequent phenomenon but it needs to be acknowledged that these studies are few in number and were done on small patient population. This case challenges the notion that presence of crystals in the synovial fluid rules out septic arthritis even in the setting of low synovial WBC count. Additionally, the presence of pseudogout in patients suffering from gout is a rare entity as well. These findings in literature are described in case reports dispersed over the past three decades. We present a case where concurrent treatment of gout, pseudogout, and septic arthritis in a patient who presented with acute hemarhtrosis.

The medical education system in United States is constantly changing. Due to recent healthcare legislation and arising need for physicians, there has been much needed innovations in graduate medical education system. Currently, there are 141 accredited medical doctor (MD)-granting institutions and 31 doctor of osteopathy (DO)-granting medical institutions. Despite of the end goal of reaching Liaison Committee on Medical Education (LCME) accredited postgraduate training program; each institution has its own unique philosophy of graduate medical program. Approaches to learning material and professor selection are also dependent on school’s average (United States Medical License Exam) scores as well as the research funding provided by the government. This article is mainly intended to educate the international students on the pathway that needs to be navigated in order to gain acceptance to medical school and the steps necessary to land a successful post-graduate resident training program. Caution must be taken to not misinterpret these steps as a guide to enter medical residency training after completing medical school abroad as these have different application system and residency selection criteria.