Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection.

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

Climate change and public health: The effects of global warming on the risk of allergies and autoimmune diseases: The effects of global warming on the risk of allergies and autoimmune diseases.

Global climate change and extreme weather events are associated with epigenetic modifications in immune cells, leading to the possible increased risk and prevalence of allergies and autoimmune diseases.

Management of Gastric Neuroendocrine Tumors: A Review.

Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.

Simple Preoperative Imaging Measurements Predict Postoperative Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: Postoperative pancreatic fistula is a potentially devastating complication after pancreatoduodenectomy (PD). The purpose of this study was to identify features on preoperative computed tomography (CT) imaging that correlate with an increased risk of postoperative pancreatic fistula (POPF). METHODS: Patients who underwent PD at our high-volume pancreatic surgery center from 2019 to 2021 were included if CT imaging was available within 8 weeks of surgical intervention. Pancreatic neck thickness (PNT), abdominal wall thickness (AWT), and intra-abdominal distance from pancreas to peritoneum (PTP) were measured by two board-certified radiologists who were blinded to the clinical outcomes. Radiographic measurements, as well as preoperative patient characteristics and intraoperative data, were assessed with univariate and multivariable analysis (MVA) to determine risk for clinically relevant POPF (CR-POPF, grades B and C). RESULTS: A total of 204 patients met inclusion criteria. Median PTP was 5.8 cm, AWT 1.9 cm, and PNT 1.3 cm. CR-POPF occurred in 33 of 204 (16.2%) patients. MVA revealed PTP > 5.8 cm (odds ratio [OR] 2.86, p = 0.023), PNT > 1.3 cm (OR 2.43, p = 0.047), soft pancreas consistency (OR 3.47, p = 0.012), and pancreatic duct size ≤ 3.0 mm (OR 4.55, p = 0.01) as independent risk factors for CR-POPF after PD. AWT and obesity were not associated with increased risk of CR-POPF. Patients with PTP > 5.8 cm or PNT > 1.3 cm were significantly more likely to suffer a major complication after PD (39.6% vs. 22.3% and 40% vs. 22.1%, p < 0.008). CONCLUSIONS: Patients with a thick pancreatic neck and increased intra-abdominal girth have a heightened risk of CR-POPF after pancreatoduodenectomy, and they experience more serious postoperative complications. We defined a simple CT scan-based measurement tool to identify patients at increased risk of CR-POPF.

Significance of Specimen Extraction Site in Minimizing Hernia Risk After Distal Pancreatectomy.

BACKGROUND: Incisional hernia (IH) results in significant morbidity to patients and financial burden to healthcare systems. We aimed to determine the incidence of IH in distal pancreatectomy (DP) patients, stratified by specimen extraction sites. METHOD: Imaging in DP patients in our institution from 2016 to 2021 were reviewed by radiologists blinded to the operative approach. Specimen extraction sites were stratified as upper midline/umbilical (UM) versus Pfannenstiel. IH was defined as fascial defect on postoperative imaging. Patients without preoperative and postoperative imaging were excluded. RESULTS: Of the 219 patients who met our selection criteria, the median age was 64 years, 54% were female, and 64% were White. The majority were minimally invasive (MIS) procedures (n = 131, 60%), of which 52% (n = 64) had a UM incision for specimen extraction, including 45 hand-assist and 19 purely laparoscopic procedures. MIS with Pfannenstiel incisions for specimen extraction was 48% (n = 58), including 44 robotic and 14 purely laparoscopic procedures. Mean follow-up time was 16.3 months (standard deviation [SD] 20.8). Follow-up for MIS procedures with UM incisions was 16.6 months (SD 21.8) versus 15.5 months (SD 18.6) in the Pfannenstiel group (p = 0.30). MIS procedures with UM incisions for specimen extraction had a 17.8 times increase in odds of developing an IH compared with MIS procedures with Pfannenstiel extraction sites (p = 0.01). The overall odds of developing an IH increased by 4% for every month of follow-up (odds ratio 1.04; p < 0.001). CONCLUSION: A Pfannenstiel incision should be performed for specimen extraction in cases with purely laparoscopic or robotic distal pancreatectomy, when feasible.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

The Gender Gap in Surgical Literature: Are We Making Progress?

INTRODUCTION: The percentage of women in surgical leadership roles is not commensurate with percent of women in field of surgery. Citation indexes are used as proxy for scholarly impact and may serve as an indicator of women's progress in academic surgery. We aimed to evaluate gender disparities in authorship of surgery manuscripts in high-impact journals. METHODS: In this bibliometric analysis of original research articles from four high-impact surgical journals from 2008 to 2010 (period A) and 2018-2020 (period B), the gender of primary and senior authors was assigned by Genderize.io. Number of citations per article was identified via Web of Science. Number of citations by gender of authors was compared across time periods. RESULTS: Of the 3575 articles (Period A = 1915; Period B = 1660), 962 (26.9%) had women as primary authors and 590 (17.2%) as senior authors. Over time, significant increases in women primary and senior authorship were noted from 22.8% to 31.7% (P < 0.001) and 13.9% (254/11,915) to 21% (336/1660), respectively (P < 0.001). Articles written with women primary authors had fewer median (interquartile range) citations than those by men as primary author in period A (39 [17-69.5] versus 42 [20.0-84.0]; P = 0.005). Gender parity was noted in period B (9 [4-19] versus 9 [4-20] citations; P = 0.307). In period A, articles written by women as both primary and senior authors had approximately 25% fewer median citations compared with those by men (34 [17-62] versus 44 [21-86]); P < 0.011), and this reached parity in period B (9 [4-20] versus 9 [4-21]); P < 0.658). CONCLUSIONS: Overall, gender authorship and citations parity are improving in high-impact surgery journals.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

BACKGROUND: To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. METHODS: In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. RESULTS: We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). CONCLUSION: Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Impact of nodal status in determining multimodal treatment strategies in non-cardia gastric cancer.

BACKGROUND: Patients with resectable noncardia gastric cancer may be subjected to perioperative chemotherapy (PEC), postoperative chemoradiation (POCR), or postoperative chemotherapy (POC). We analyzed these treatment strategies to determine optimal therapy based on nodal status. METHOD: The National Cancer Database was used to identify patients with resected noncardia gastric cancer (2004-2016). Patients were stratified based on clinical nodal status-negative (cLN-), positive (cLN+) and pathological nodal status (pLN-, pLN+). In cLN- patients who underwent upfront resection and were upstaged to pLN+, POC, and POCR were compared. Overall survival (OS) with PEC, POCR, and POC were compared in cLN- and cLN+. RESULTS: We identified 6142 patients (cLN-: 3831; cLN+: 2311). In cLN- patients who underwent upfront resection (N = 3423), 69% were upstaged to pLN+ disease (N = 2499; POCR = 1796, POC = 703). On MVA, POCR was associated with significantly improved OS when compared to POC (hazard ratio [HR]: 0.75; p < 0.001). In patients with cLN- disease (PEC = 408; POCR = 2439; POC = 984), PEC(HR: 0.77; p = 0.01) and POCR(HR: 0.81; p < 0.001) were associated with improved OS compared with POC. In cLN+ group (PEC = 452; POCR = 1284; POC = 575), POCR was associated with improved OS compared with POC (HR: 0.81; p < 0.01), and trend towards improved OS was noted when PEC(HR: 0.83; p = 0.055) was compared with POC. CONCLUSION: Postoperative chemoradiation may be the preferred treatment strategy over postoperative chemotherapy in non-cardia gastric cancer patients who receive upfront resection and are upstaged from clinically node negative to pathologically node positive disease.

Does non-metastatic gastric cancer of the cardia warrant a different treatment strategy?

BACKGROUND: Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy. METHOD: We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed. RESULTS: We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort. CONCLUSION: OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.

Early experience with robotic central pancreatectomy with patient-reported outcomes and comparison with open central pancreatectomy.

BACKGROUND: Robotic central pancreatectomy (CP) has emerged in recent years as a noninferior approach to open CP and may offer improved patient-reported outcomes and reduction in incisional hernias. METHODS: All patients who underwent open and robotic CP between (2013 and 2022) were selected, and perioperative outcomes were analyzed. Patients who underwent robotic CP were interviewed over the phone to assess patient-reported postoperative outcomes. RESULTS: A total of 18 CP operations (56%-open vs. 44%-robotic) were identified. The overall median age was 67 years (interquartile range: 60-72), and 50% (n = 9) of patients were female. Median length of surgery was statistically longer for robotic CP (411 vs. 138 min, p = 0.002); all other intraoperative variables were similar. Postoperatively, a similar number of patients in the open and robotic cohorts developed clinically significant postoperative pancreatic fistulas (37.5% vs. 30%, p = 1) and major complications (37.5% vs. 20%, p = 0.60), respectively. No patients in the robotic cohort developed an incisional hernia, compared to 40% (n = 4) in open (p = 0.08). All patients returned to a baseline level of activity and reported a high quality of life. CONCLUSION: With the exception of longer operative times, robotic CP is a noninferior, definitive resection technique for select lesions of the middle pancreas. Additionally, the robotic approach may result in a reduction in incisional hernia development.

Surgical approach to microwave and radiofrequency liver ablation for hepatocellular carcinoma and colorectal liver metastases less than 5 cm: a systematic review and meta-analysis.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5 cm. METHODS: A systematic review was conducted across seven databases, including PubMed, Embase, and Cochrane, to identify all comparative studies between 1937 and 2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data. RESULTS: From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC and CRLM lesions less than 5 cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors < 3 cm. CONCLUSION: The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.

SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

Landmark Series: Importance of Pancreatic Resection Margins.

An important goal of cancer surgery is to achieve negative surgical margins and remove all disease completely. For pancreatic neoplasms, microscopic margins may remain positive despite gross removal of the palpable mass, and surgeons must then consider extending resection, even to the point of completion pancreatectomy, an option that renders the patient with significant adverse effects related to exocrine and endocrine insufficiency. Counterintuitively, extending resection to ensure clear margins may not improve patient outcome. Furthermore, the goal of improving survival by extending the resection may not be achieved, as an initial positive margin may indicate more aggressive underlying tumor biology. There is a growing body of literature on this topic, and this landmark series review will examine the key publications that guide our management for resection of pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasms, and pancreatic neuroendocrine tumors.

The Impact of Carbohydrate Antigen 19-9 on Survival in Patients with Clinical Stage I and II Pancreatic Cancer.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB). METHODS: The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I-II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported. RESULTS: Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98 U/mL. Stage I-II patients with CA19-9 < 98 U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98 U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98 U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%). CONCLUSIONS: Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I-II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9.

Defining the role of systemic therapy in resectable pancreatic acinar cell carcinoma.

INTRODUCTION: Following resection of pancreatic acinar cell carcinoma (PACC) distant recurrence remains high. We utilized the national cancer database (NCDB) to evaluate the role of systemic therapy in early-stage resected PACC. METHODS: We queried the NCDB registry from 2004 to 2015 for patients with pathologic stage I-IIB PACC. For each stage, patients who underwent surgery alone (SA) were compared to patients who received systemic and/or radiation therapy in addition to surgery (surgery + therapy [S + T]). RESULTS: A total of 271 patients (101 pI, 81 pIIA, and 89 pIIB) were analyzed. Of all clinically node positive patients (n = 41), the majority (n = 32, 78%) had node-positive disease at resection (pIIB). SA was performed in 112 patients (41.3%), whereas 159 (58.7%) patients received S + T. There was no difference in overall survival (OS) between S + T and SA with respect to pI or pIIA disease. In pIIB disease, S + T was associated with improved OS compared to SA (34.9 vs. 16.9 months, p = 0.031). Single-agent chemotherapy was associated with improved OS for pIIB disease when compared to SA (hazard ratio: 0.38, 95% confidence interval: 0.16, 0.83). CONCLUSION: In resectable PACC, the survival benefit of adjuvant therapy is limited to pathologic stage IIB disease. This benefit is evident even in patients treated with single-agent chemotherapy.

A review of hepatic epithelioid hemangioendothelioma-Analyzing patient characteristics and treatment strategies.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence. METHODS: The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan-Meier method was used to create OS curves and compared using the log-rank test. RESULTS: We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson-Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson-Deyo score (score 1: HR, 2.28; p < 0.001 and score ≥2: HR, 2.76; p = 0.011) were associated with worse OS. CONCLUSION: Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease.