Faculty Bibliography

OBJECTIVES/OBJECTIVE:Most patients with intraductal papillary mucinous neoplasms (IPMNs) are diagnosed with a solitary lesion; however, the presence of skip lesions, not appreciable on imaging, has been described. Postoperatively, these missed lesions can continue to grow and potentially become cancerous. Intraoperative pancreatoscopy (IOP) may facilitate detection of such skip lesions in the remnant gland. The aim of this scoping review was to appraise the evidence on the role of IOP in the surgical management of IPMNs. MATERIALS AND METHODS/METHODS:Studies reporting on the use of IOP during IPMN surgery were identified through searches of the PubMed, Embase, and Scopus databases. Data extracted included IOP findings, surgical plan modifications, and patient outcomes. The primary outcome of interest was the utility of IOP in surgical decision making. RESULTS:Ten studies reporting on the use of IOP for IPMNs were identified, representing 147 patients. A total of 46 skip lesions were identified by IOP. Overall, surgical plans were altered in 37% of patients who underwent IOP. No IOP-related complications were reported. CONCLUSIONS:The current literature suggests a potential role of integration of IOP into the management of patients with IPMNs. This tool is safe and feasible and can result in changes in surgical decision making.

INTRODUCTION/BACKGROUND:There is no consensus regarding the role of primary tumor resection for patients with metastatic pancreatic neuroendocrine tumors (panNET). We assessed surgical treatment patterns and evaluated the survival impact of primary tumor resection in patients with metastatic panNET. METHODS:Patients with synchronous metastatic nonfunctional panNET in the National Cancer Database (2004-2016) were categorized based on whether they underwent primary tumor resection. We used logistic regressions to assess associations with primary tumor resection. We performed survival analyses with Kaplan-Meier survival functions, log-rank test, and Cox proportional hazard regression within a propensity score matched cohort. RESULTS:In the overall cohort of 2613 patients, 68% (n = 839) underwent primary tumor resection. The proportion of patients who underwent primary tumor resection decreased over time from 36% (2004) to 16% (2016, p < 0.001). After propensity score matching on age at diagnosis, median income quartile, tumor grade, size, liver metastasis, and hospital type, primary tumor resection was associated with longer median overall survival (OS) (65 vs. 24 months; p < 0.001) and was associated with lower hazard of mortality (HR: 0.39, p < 0.001). CONCLUSION/CONCLUSIONS:Primary tumor resection was significantly associated with improved OS, suggesting that, if feasible, surgical resection can be considered for well-selected patients with panNET and synchronous metastasis.

Pancreatic ductal adenocarcinoma is the third-leading cause of all cancer-related deaths in the US. While 20% of patients have resectable disease at diagnosis, improved control of systemic disease using effective chemotherapeutic regimens allows for aggressive operations involving complex vascular resection and reconstruction. A pancreas protocol computed tomography (PPCT) is the gold standard imaging modality in determining local resectability (degree of tumor-vessel involvement), however, it is limited by the inter-operator variability. While post-processing-3D-rendering helps, it does not allow for real-time dynamic assessment of resectability. A recent development in post-process-rendering called cinematic rendering (CR) overcomes this by utilizing advanced light modeling to generate photorealistic 3D images with enhanced details. Cinematic rendering allows for nuanced visualization of areas of interest. Our preliminary experience, as one of the first centers to incorporate the routine use of CR, has proven very useful in surgical planning. For local determination of resectability, vascular mapping allows for accurate assessment of major arteries and the portovenous system. For the portovenous anatomy it assists in determining the optimal surgical approach (extent of resection, appropriate technique for reconstruction, and need for mesocaval shunting). For arterial anatomy, vessel encasement either represents dissectible involvement via periadventitial dissection or true vessel invasion that is unresectable. CR could potentially provide superior ability than traditional PPCT to discern between the two. Additionally, CR allows for better 3D visualization of arterial anatomic variants which, if not appreciated preoperatively, increases risk of intraoperative ischemia and postoperative complications. Lastly, CR could help avoid unnecessary surgery by enhanced identification of occult metastatic disease that is metastatic disease that is otherwise not appreciated on a standard PPCT.

OBJECTIVES/OBJECTIVE:We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN/METHODS:Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING/METHODS:Five U.S. medical centers. PATIENTS/METHODS:Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS/METHODS:Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS/RESULTS:The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival ,frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS:Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

BACKGROUND:Consensus guidelines discourage resection of poorly differentiated pancreatic neuroendocrine carcinoma (panNEC) given its association with poor long-term survival. This study assessed treatment patterns and outcomes for this rare malignancy using the National Cancer Database (NCDB). METHODS:Patients with non-functional pancreatic neuroendocrine tumors in the NCDB (2004-2016) were categorized based on pathologic differentiation. Logistic and Cox proportional hazard regressions identified associations with resection and overall survival (OS). Survival was compared using Kaplan-Meier and log-rank tests. RESULTS:Most patients (83%) in the cohort of 8560 patients had well-differentiated tumors (panNET). The median OS was 47 months (panNET, 63 months vs panNEC, 17 months; p < 0.001). Surgery was less likely for older patients (odds ratio [OR], 0.97), patients with panNEC (OR, 0.27), and patients with metastasis at diagnosis (OR, 0.08) (all p < 0.001). After propensity score-matching of these factors, surgical resection was associated with longer OS (82 vs 29 months; p < 0.001) and a decreased hazard of mortality (hazard ratio [HR], 0.37; p < 0.001). Surgery remained associated with longer OS when stratified by differentiation (98 vs 41 months for patients with panNET and 36 vs 8 months for patients with panNEC). Overall survival did not differ between patients with panNEC who underwent surgery and patients with panNET who did not (both 39 months; p = 0.294). CONCLUSIONS:Poorly differentiated panNEC exhibits poorer survival than well-differentiated panNET. In the current cohort, surgical resection was strongly and independently associated with improved OS, suggesting that patients with panNEC who are suitable operative candidates should be considered for multimodality therapy, including surgery.

Background/UNASSIGNED:The omentum provides abundant lymphatic tissue with reliable vascular anatomy, representing an ideal donor for vascularized lymph node transfer without risk for donor site lymphedema. We describe a novel, robotically assisted approach for omental flap harvest. Methods/UNASSIGNED:All patients undergoing robotically assisted omentum harvest for vascularized lymph node transfer from 2017 to 2019 were identified. Patient demographics, intraoperative variables, and postoperative outcomes were reviewed. Results/UNASSIGNED:, respectively. Indications for lymph node transfer were upper extremity lymphedema following mastectomy, radiation, and lymphadenectomy (60.0%); congenital unilateral lower extremity lymphedema (20.0%); and bilateral lower extremity/scrotal lymphedema following partial penectomy and bilateral inguinal/pelvic lymphadenectomy (20.0%). Four patients (80.0%) underwent standard robotic harvest, whereas 1 patient underwent single-port robotic harvest. The average number of port sites was 4.4. All patients underwent omentum flap transfer to 2 sites; in 2 cases, the flap was conjoined, and in 3 cases, the flap was segmented. The average overall operative time was 9:19. The average inpatient hospitalization was 5.2 days. Two patients experienced cellulitis, which is resolved with oral antibiotics. There were no major complications. All patients reported subjective improvement in swelling and softness of the affected extremity. The average follow-up was 8.8 months. Conclusions/UNASSIGNED:Robotically assisted omental harvest for vascularized lymph node transfer is a novel, safe, and viable minimally invasive approach offering improved intra-abdominal visibility and maneuverability for flap dissection.

BACKGROUND:Low-grade fibromyxoid sarcoma (LGFMS) is a rare fibroblastic tumor often involving deep tissue of trunk and lower extremities in young to middle-aged patients. Rarely, LGFMS can occur in other sites including head and neck, chest, abdomen and female reproductive system. Three cases of LGFMS in mesentery of small intestine have been reported and all have conventional histologic features. Herein we reported a unique case of LGFMS in mesentery of small intestine. CASE PRESENTATION/METHODS:A 43 year-old male with chief complaint of lower back pain for 4 years presented to our hospital. Physical exam reveal a firm, non-tender, non-distended, mobile large abdominal mass, which was shown on abdominal CT as a 10 cm retroperitoneal tumor. Biopsy revealed a spindle cell neoplasm in a myxoid background with a delicate vascular network. Tumor resection was performed. Gross examination of the resected specimen showed a 10.8 cm, tan-white, smooth, firm, lobulated mesenteric mass with bulging and gelatinous cut surface and confined within small bowel serosa. Microscopic examination demonstrated foci epithelioid cords and whorls with prominent atypia, in additional of regular, bland-appearing spindle cells in a fibrous and myxoid stroma and osseous metaplasia. The tumor cells stained diffusely positive for DOG1 with moderate staining density, and diffusely and strongly positive for MUC4. Rearrangement involving FUS (16p11.2) gene was identified with break-apart probe and confirmed by Anchored Multiplex PCR. A final diagnosis of low-grade fibromyxoid sarcoma was rendered. CONCLUSION/CONCLUSIONS:Our case highlights the importance of including LGFMS in the differential diagnosis of mesenteric tumors and the DOG1 positivity which could represent a potential diagnostic pitfall.