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Recent clinical successes with immunotherapy have resulted in expanding indications for cancer therapy. To enhance antitumor immune responses, and to better choose specific strategies matched to patient and tumor characteristics, genomic-driven precision immunotherapy will be necessary. Herein, we explore the role that tumor gene-expression profiling (GEP) may have in the prediction of an immunotherapeutic response. Genetic markers associated with response to immunotherapy are addressed as they pertain to the tumor genomic landscape, the extent of DNA damage, tumor mutational load and tumor-specific neoantigens. Furthermore, genetic markers associated with resistance to checkpoint blockade and relapse are reviewed. Finally, the utility of GEP to identify new tumor types for immunotherapy and implications for combinatorial strategies are summarized.

Background: Surgical and adjuvant management of mucinous cystic neoplasms (MCNs) lacks formal guidelines and data is limited to institutional studies. Factors associated with receipt of adjuvant therapy and any associated impact on survival remain to be clarified. In the absence of other data, guidelines that recommend adjuvant chemotherapy for invasive pancreatic adenocarcinoma have been extrapolated to MCN., Patients and Methods: The National Cancer Database (2004-2019) was utilized to identify all patients that underwent pancreatic resection for invasive MCNs. Patients that received neoadjuvant therapy or did not undergo lymphadenectomy were excluded. Patient, tumor, and treatment factors associated with survival were assessed., Results: For 161 patients with invasive MCN, median overall survival (OS) was 133 months and 45% of patients received adjuvant therapy. Multivariable analysis demonstrated that poorly differentiated tumors [odds ratio (OR) 4.19, 95% confidence interval (CI) 1.47-11.98; p = 0.008] and positive lymph node status (OR 2.67, 95% CI 1.02-6.98; p = 0.042) were independent predictors of receiving adjuvant therapy. Lymph node positivity [hazard ratio (HR) 2.90, 95% CI 1.47-5.73; p = 0.002], positive margins (HR 5.28, 95% CI 2.28-12.27; p < 0.001), and stage III disease (HR 12.46, 95% CI 1.40-111.05; p = 0.024) were associated with worse OS. Receipt of adjuvant systemic therapy was independently associated with decreased risk of mortality in node positive patients (HR 0.23, 95% CI 0.10-0.69; p = 0.002). Survival was not associated with adjuvant therapy in patients with negative lymph nodes or margin negative status., Conclusion: In contrast to pancreatic ductal adenocarcinoma (PDAC), where adjuvant therapy improves OS for every tumor stage, surgery alone for invasive MCN is not associated with improved OS compared with surgery plus adjuvant therapy in node-negative patients. Surgery alone is likely sufficient for a subset of invasive MCN., (© 2024. The Author(s).)

Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation., Competing Interests: Disclosure A.V. Maker is an inventor of record on the following pending or issued patent: WO2018183603A1 (PCT/US2018/025,027). T. Pollini and L. Todeschini have no conflict of interest. Funding Authors acknowledge the support of the Inner Child Foundation and the Shorenstein Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Synoptic operative reports (SORs) are checklists or templates that contain standardized elements of an operation. These elements are associated with standardized inclusion of critical elements of the operative report that translate into numerous potential benefits. Whereas SORs for melanoma, breast, and colorectal cancer surgery have already been widely implemented, similar templates for hepato-pancreato-biliary (HPB) cancer surgery are currently lacking., Methods: An anonymous voluntary online survey was distributed to HPB attendings and fellows at HPB and complex general surgical oncology (CGSO) fellowship programs., Results: The 54 participants in this study comprised 31 (57%) HPB surgery attendings, 15 (28%) HPB surgery fellows, and 8 (15%) CGSO fellows. Notably, only six (11%) participants reported consistent use of an HPB SOR. The most commonly reported barriers to SOR uptake were the "lack of a readily available template" (55%) and the "lack of consensus/guidelines" (49%). Despite these limiting factors, a majority of respondents indicated a strong willingness to use a standardized and readily available HPB SOR (mean, 4.13/5 ± 1.23). This interest did not differ between attendings and fellows (p = 0.52) or between the participants stratified by surgical experience (p = 0.58). Finally, the participants were provided a comprehensive list of possible elements to incorporate into a standardized pancreatic and hepatobiliary SOR. After the exclusion of elements with less than 75% agreement, the pancreatic SORs included 17 (57%) of 30 possible elements, and the hepatobiliary SORs included 19 (76%) of 25 possible elements., Conclusion: Broad consensus on several elements of the HPB SOR suggests that uptake should be accelerated in HPB surgery., (© 2024. Society of Surgical Oncology.)

Background: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC., Methods: Retrospective analysis of single-institution data., Results: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease., Conclusions: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained., (© 2024. The Author(s).)

Pancreatoblastoma is perceived to be aggressive in adults; however, data are limited due to the rarity of the disease. We benchmarked clinico-pathologic characteristics, outcomes, and survival of adult patients with pancreatoblastoma to a comparable PDAC cohort using the National Cancer Database (NCDB). This study included 301,204 patients: 35 with pancreatoblastoma and 301,169 PDAC patients. Pancreatoblastoma patients were younger than PDAC patients (56 vs. 69 years, p < 0.001). More pancreatoblastoma patients were managed at academic institutions (63.0% vs. 40.7%, p = 0.047). The most frequent primary site was the head and the neck of the pancreas. There were no differences in tumor size (4.2 cm vs. 3.7 cm, p = 0.828), lymph node positivity (14.3% vs. 26.4%, p = 0.103), or metastasis at time of diagnosis (31.4% vs. 46.1%, p = 0.081). The majority of pancreatoblastoma patients underwent resection compared to a minority of PDAC patients (69.7% vs. 15.5%, p < 0.001). Time from diagnosis to surgery was longer for pancreatoblastoma patients (33 vs. 14 days, p = 0.030). Pancreaticoduodenectomy was the most common type of resection in the pancreatoblastoma and PDAC groups (47.8% vs. 67.7%, p = 0.124). Among resected patients, pancreatoblastoma patients were less likely to receive radiation (4.8% vs. 37.0%, p = 0.002), but the use of chemotherapy was similar to PDAC patients (60.9% vs. 70.7%). After matching, median overall survival was longer for pancreatoblastoma than PDAC (59.8 months vs. 15.2 months, p = 0.014).

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies., Significance: This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.

Background: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy., Case Presentation: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free., Conclusions: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Despite significant advancements in the treatment of patients with colorectal liver metastases (CRLMs), only a minority will experience long-term survival. This study aimed to determine the effect of chemotherapy (CT) and immunotherapy (IT) compared with that of CT alone on patient survival after surgical resection., Methods: Patients undergoing curative-intent liver resection followed by adjuvant systemic therapy for stage IV colon cancer were identified using the National Cancer Database. Patients were stratified into type of therapy (CT alone vs CT + IT) and microsatellite status. Propensity score-weighted analysis was performed through 1:1 matching based on the nearest neighbor method., Results: Of 9943 patients who underwent resection of CRLMs, 7971 (80%) received systemic adjuvant therapy. Of 7971 patients, 1432 (18%) received a combination of CT and IT. Microsatellite status was not associated with overall survival (OS). Adjuvant CT + IT was associated with increased 3-year OS compared with that of CT alone in both the unmatched cohort (55% vs 48%, respectively; P < .001) and matched cohort (52% vs 48%, respectively; P = .050). On multivariate analysis, older age, positive resection margins, and KRAS mutation were independent predictors of poor survival, whereas the administration of adjuvant CT + IT was an independent predictor of improved survival., Conclusion: IT combined with CT was associated with improved survival compared with that of CT alone after curative-intent resection of CRLMs, regardless of microsatellite instability status. Clinical trials to determine optimal patient selection, IT regimen, and long-term efficacy to improve outcomes of patients with CRLMs are warranted., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Textbook oncologic outcome (TOO) is a benchmark for high-quality surgical cancer care but has not been studied at safety-net hospitals (SNH). The study sought to understand how SNH burden affects TOO achievement in colorectal cancer., Methods: The National Cancer Database was queried for colorectal cancer patients who underwent resection for stage I-III plus stage IV with liver-only metastases (2010-2019). TOO was defined as R0 resection, AJCC-compliant lymphadenectomy (>12 nodes), no prolonged LOS, no 30-day mortality/readmission, and receipt of stage-appropriate adjuvant chemotherapy., Results: Of 487,195 patients, 66.7% achieved TOO. Lower achievement was explained by adequate lymphadenectomy (87.3%), non-prolonged LOS (76.3%), and receipt of adjuvant chemotherapy in stage III (60.3%) and IV (54.1%). Treatment at high burden hospitals (HBH, >10% Medicaid/uninsured) was a predictor of non-TOO (Stage I/II: OR 0.83, III: OR 0.86, IV: OR 0.83; all p < 0.001). Achieving TOO was associated with decreased mortality (Stage I/II: HR 0.49, III: HR 0.48, IV: HR 0.57; all p < 0.001), and HBH treatment was a predictor of mortality (Stage I/II: HR 1.09, III: HR 1.05, IV: HR 1.07; all p < 0.05)., Conclusions: Treatment at higher SNH burden hospitals was associated with less frequent TOO achievement and increased mortality. Quality improvement targets include receipt of adjuvant chemotherapy and avoidance of prolonged LOS., (© 2023 Wiley Periodicals LLC.)

Background: Tertiary medical centers in the USA provide specialized, high-volume surgical cancer care, contributing standards for quality and outcomes. For the most vulnerable populations, safety-net hospitals (SNHs) remain the predominant provider of both complex and routine healthcare needs. The objective of this study was to evaluate access to and quality of surgical oncology care within SNHs., Methods: A comprehensive and systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane Library databases to identify all studies (January 2000-October 2021) reporting the delivery of surgical cancer care at SNHs in the USA (PROSPERO #CRD42021290092). These studies describe the process and/or outcomes of surgical care for gastrointestinal, hepatopancreatobiliary, or breast cancer patients seeking treatment at SNHs., Results: Of 3753 records, 37 studies met the inclusion criteria. Surgical care for breast cancer (43%) was the most represented, followed by colorectal (30%) and hepatopancreatobiliary (16%) cancers. Financial constraints, cultural and language barriers, and limitations to insurance coverage were cited as common reasons for disparities in care within SNHs. Advanced disease at presentation was common among cancer patients seeking care at SNHs (range, 24-61% of patients). Though reports comparing cancer survival between SNHs and non-SNHs were few, results were mixed, underscoring the variability in care seen across SNHs., Conclusions: These findings highlight barriers in care facing many cancer patients. Continued efforts should address improving both access and quality of care for SNH patients. Future models include a transition away from a two-tiered system of resourced and under-resourced hospitals toward an integrated cancer system., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables., Methods: Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed., Results: Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78., Conclusions: In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted., Methods: Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival., Results: Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment., Conclusions: CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic review and meta-analysis is to define the pooled rate of malignancy for MCN., Methods: A systematic review of eligible studies published between 2000 and 2021 was performed on PubMed and Embase. Primary outcome was rate of malignancy. Data regarding high-risk features, including cyst size and mural nodules, were collected and analyzed., Results: A total of 40 studies and 3292 patients with resected MCN were included in the final analysis. The pooled rate of malignancy was 16.1% (95%CI 13.1-19.0). The rate of malignant MCN in studies published before 2012 was significantly higher than that of studies published after recent guidelines were published (21.0% vs 14.9%, p < 0.001). Malignant MCN were larger than benign (mean difference 25.9 mm 95%CI 14.50-37.43, p < 0.001) with a direct correlation between size and presence of malignant MCN (R2 = 0.28, p = 0.020). A SROC identified a threshold of 65 mm to be associated with the diagnosis of malignant MCN. Presence of mural nodules was associated with the diagnosis of a malignant MCN (OR = 4.34, 95%CI 3.00-6.29, p < 0.001)., Conclusion: Whereas guidelines recommend resection of all MCN, the rate of malignancy in resected MCN is 16%, implying that surveillance has a role in most cases, and that surgical selection criteria are warranted. Size and presence of mural nodules are significantly associated with an increased risk of malignant degeneration, small MCN and without mural nodules can be considered for surveillance., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

We have shown that activin A (activin), a TGF-β superfamily member, has pro-metastatic effects in colorectal cancer (CRC). In lung cancer, activin activates pro-metastatic pathways to enhance tumor cell survival and migration while augmenting CD4+ to CD8+ communications to promote cytotoxicity. Here, we hypothesized that activin exerts cell-specific effects in the tumor microenvironment (TME) of CRC to promote anti-tumoral activity of immune cells and the pro-metastatic behavior of tumor cells in a cell-specific and context-dependent manner. We generated an Smad4 epithelial cell specific knockout ( Smad4 -/-) which was crossed with TS4-Cre mice to identify SMAD-specific changes in CRC. We also performed IHC and digital spatial profiling (DSP) of tissue microarrays (TMAs) obtained from 1055 stage II and III CRC patients in the QUASAR 2 clinical trial. We transfected the CRC cells to reduce their activin production and injected them into mice with intermittent tumor measurements to determine how cancer-derived activin alters tumor growth in vivo. In vivo, Smad4-/- mice displayed elevated colonic activin and pAKT expression and increased mortality. IHC analysis of the TMA samples revealed increased activin was required for TGF-β-associated improved outcomes in CRC. DSP analysis identified that activin co-localization in the stroma was coupled with increases in T-cell exhaustion markers, activation markers of antigen presenting cells (APCs), and effectors of the PI3K/AKT pathway. Activin-stimulated PI3K-dependent CRC transwell migration, and the in vivo loss of activin lead to smaller CRC tumors. Taken together, activin is a targetable, highly context-dependent molecule with effects on CRC growth, migration, and TME immune plasticity.

Background: Despite multiple studies and randomized trials, there remains controversy over whether drains should be placed, and if so for how long, after pancreas resection. The aim was to determine if post-pancreatectomy drain placement and timing of drain removal were associated with differences in infectious outcomes and, if so, which specific procedures and infectious sites were most at risk., Methods: The ACS-NSQIP targeted pancreatectomy database was utilized to identify patients who underwent pancreatectomies between 2015 and 2020 with postoperative drain placement for retrospective cohort analysis. A propensity score matching analyses was conducted to determine associations between drain placement and surgical site infections (SSI)., Results: Of 39,057 pancreatic resections, 66.4% were proximal pancreatectomies, and 33.6% were distal pancreatectomies. After propensity score matching, drain placement was not associated with significantly lower rates of superficial SSI (7% vs 9%, p = 0.755) or organ/space SSI (17% vs 16%, p = 0.647) after proximal pancreatectomy. After distal pancreatectomy, drain placement was associated with higher rates of organ/space SSI (12% vs 9%, p = 0.010). Drain removal on or after postoperative day 3 was significantly associated with higher rates of SSI in both proximal and distal pancreatectomy., Conclusions: Drain placement is associated with an increased rate of organ/space SSI after distal pancreatectomy and not after pancreaticoduodenectomy. When drains are utilized, early removal is associated with a reduction of SSI after all types of pancreatectomy. In surgical units where post-pancreatectomy SSI is a concern, selective drain placement for high-risk glands or after distal pancreatectomy, combined with early drain removal, may be considered., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Hand-assisted laparoscopic distal pancreatectomy (HALDP) is suggested to offer similar outcomes to pure laparoscopic distal pancreatectomy (LDP). However, given the longer midline incision, it is unclear whether HALDP increases the risk of postoperative hernia. Our aim was to determine the risk of postoperative incisional hernia development after HALDP., Methods: We retrospectively collected data from patients undergoing HALDP or LDP at a single center (2012-2020). Primary endpoints were postoperative incisional hernia and operative time. All patients had at minimum six months of follow-up. Outcomes were compared using unadjusted and multivariable regression analyses., Results: Ninety-five patients who underwent laparoscopic distal pancreatectomy were retrospectively identified. Forty-one patients (43%) underwent HALDP. Patients with HALDP were older (median, 67 vs. 61 years, p = 0.02). Sex, race, Body Mass Index (median, 27 vs. 26), receipt of neoadjuvant chemotherapy, gland texture, wound infection rates, postoperative pancreatic fistula, overall complications, and hospital length-of-stay were similar between HALDP and LDP (all p > 0.05). In unadjusted analysis, operative times were shorter for HALDP (164 vs. 276 min, p < 0.001), but after adjustment, did not differ significantly (MR 0.73; 0.49-1.07, p = 0.1). Unadjusted incidence of hernia was higher in HALDP versus LDP (60% vs. 24%, p = 0.004). After adjustment, HALDP was associated with an increased odds of developing hernia (OR 7.52; 95% CI 1.54-36.8, p = 0.014). After propensity score matching, odds of hernia development remained higher for HALDP (OR 4.62; 95% CI 1.28-16.65, p = 0.031) p = 0.03)., Conclusions: Compared with LDP, HALDP was associated with increased likelihood of postoperative hernia with insufficient evidence that HALDP shortens operative times. Our results suggest that HALDP may not be equivalent to LDP., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Modern series report a prevalence of pancreatic cysts in the general population of up to 50% in prospective studies. Of these, about half will be pancreatic cystic neoplasms (PCNs) that have varying degrees of malignant potential. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most common PCNs and are known predecessors of pancreatic adenocarcinoma. Critically, they are one of the only radiographically identifiable precursors of pancreatic cancer and thus provide an opportunity for early cancer detection and surgical resection with curative intent. The combination of high prevalence and potential for malignant degeneration underscore the relevance of discussing the best management of IPMNs and improving the existing standard of care. Landmark data on IPMN prevalence, guidelines, surveillance, biomarkers, and immune landscape are highlighted., (© 2023. The Author(s).)

Background: Although hypertension requiring medication (HTNm) is a well-known cardiovascular comorbidity, its association with postoperative outcomes is understudied. This study aimed to evaluate whether preoperative HTNm is independently associated with specific complications after pancreaticoduodenectomy., Study Design: Adults undergoing elective pancreaticoduodenectomy were included from the 2014-2019 NSQIP-targeted pancreatectomy dataset. Multivariable regression models compared outcomes between patients with and without HTNm. Endpoints included significant complications, any complication, unplanned readmissions, length of stay (LOS), clinically relevant postoperative pancreatic fistula (CR-POPF), and cardiovascular and renal complications. A subgroup analysis excluded patients with diabetes, heart failure, chronic obstructive pulmonary disease, estimated glomerular filtration rate from serum creatinine (eGFRCr) < 60 ml/min per 1.73 m 2 , bleeding disorder, or steroid use., Results: Among 14,806 patients, 52% had HTNm. HTNm was more common among older male patients with obesity, diabetes, congestive heart failure, chronic obstructive pulmonary disease, functional dependency, hard pancreatic glands, and cancer. After adjusting for demographics, preoperative comorbidities, and laboratory values, HTNm was independently associated with higher odds of significant complications (aOR 1.12, p = 0.020), any complication (aOR 1.11, p = 0.030), cardiovascular (aOR 1.78, p = 0.002) and renal (aOR 1.60, p = 0.020) complications, and unplanned readmissions (aOR 1.14, p = 0.040). In a subgroup analysis of patients without major preoperative comorbidity, HTNm remained associated with higher odds of significant complications (aOR 1.14, p = 0.030) and cardiovascular complications (aOR 1.76, p = 0.033)., Conclusions: HTNm is independently associated with cardiovascular and renal complications after pancreaticoduodenectomy and may need to be considered in preoperative risk stratification. Future studies are necessary to explore associations among underlying hypertension, specific antihypertensive medications, and postoperative outcomes to investigate potential risk mitigation strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Malignant peritoneal mesothelioma (MPM) is a rare disease with a historically poor prognosis. Given the emergence of effective therapies, a contemporary analysis of MPM incidence and survival is warranted. Methods: The SEER-18 registry dataset was analyzed (2000−2018). Age-adjusted annual incidence was stratified by sex and histology. Joinpoint regression was used to estimate annual percent change (APC) in incidence. Multivariable cox proportional hazards models were used to investigate survival trends. Results: Of 1689 MPM cases, most were male (55.4%), >50 years (80.0%), and white (75.2%). Age-adjusted incidence of MPM remained stable over time, with an average annual incidence of 1.02 cases/million. Epithelioid histology increased by 240% (APC 2.6; 95% CI: 0.7, 4.5), while incidence of undefined histology decreased significantly (APC −2.1; 95% CI: −3.1, −1.1). Cases treated with cancer-directed surgery increased from 27% to 43%. Overall median age-standardized survival was 11.6 months. Median age-standardized survival was 16.6 months for epithelioid histology but 2.0 months for sarcomatoid histology. Diagnosis in recent years (2015−2018 HR 0.51; 95% CI: 0.38, 0.67) and receipt of cancer-directed surgery (HR 0.84; 95% CI: 0.72, 0.98) were associated with improved survival. Conclusions: Although the overall incidence of MPM remained stable, recognition of epithelioid histology increased. Concurrent with an increase in cancer-directed surgery, MPM survival has improved.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) have gained substantial attention because they represent one of the only radiographically identifiable precursors of invasive pancreatic ductal adenocarcinoma. Although most of these neoplasms have low-grade dysplasia and will remain indolent, a subset of IPMNs will progress to invasive cancer. The role of the immune system in the progression of IPMNs is unclear, but understanding its role could reveal the mechanism of neoplastic progression and targets for immunotherapy to inhibit progression or treat invasive disease. The available evidence supports a shift in the immune composition of IPMNs during neoplastic progression. Although low-grade lesions contain a high proportion of effector T cells, high-grade IPMNs, and IPMNs with an associated invasive carcinoma lose the T-cell infiltrate and are characterised by a predominance of immunosuppressive elements. Several possible therapeutic strategies emerge from this analysis that are unique to IPMNs and its microbiome., Competing Interests: Declaration of interests The Department of General and Pancreatic Surgery at the University of Verona received funding from the Italian Ministry of Health (Grant FIMP-CUP J38D19000690001). GP reports funding from Associazione Italiana Ricerca sul Cancro (IG 2021-26201). RH is under a license agreement between Thrive Earlier Detection, a subsidiary of Exact Sciences, and the Johns Hopkins University. AVM's research in tumour immunology is funded through the National Institutes of Health Method To Extend Research in Time award (R37CA238435), and AVM is an inventor who has the following pending or issued patents: WO2018183603A1 (PCT/US2018/025027) and US9757457B2., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Limited contemporary data has compared similarities and differences between total laparoscopic (LDP), hand-assisted (HALDP), and open distal pancreatectomy (ODP). This study aimed to examine similarities and differences in outcomes between these three approaches in a contemporary cohort. Methods: Patients undergoing elective LDP, HALDP, and ODP in the NSQIP dataset (2014−2019) were included. Descriptive statistics and multivariate regression analyses were employed to compare postoperative outcomes. Results: Among 5636 patients, 33.9% underwent LDP, 13.1% HALDP, and 52.9% ODP. Compared with the LDP approach, surgical site infections were more frequent in HALDP and ODP approaches (1.2% vs. 2.6% vs. 2.8%, respectively, p < 0.01). After adjustment, the LDP approach was associated with a significantly lower likelihood of surgical site infection (OR 0.25, p = 0.03) when compared to ODP. There was no difference in the likelihood of surgical site infection when HALDP was compared to ODP (OR 0.59, p = 0.40). Unadjusted operative times were similar between approaches (LDP = 192 min, HALDP = 193 min, ODP = 191 min, p = 0.59). After adjustment, the LDP approach had a longer operative time (+10.3 min, p = 0.04) compared to ODP. There was no difference in the adjusted operative time between HALDP and ODP approaches (+5.4 min, p = 0.80). Conclusions: Compared to ODP, LDP was associated with improved surgical site infection rates and slightly longer operative times. There was no difference in surgical site infection rates between ODP and HALDP. Surgeon comfort and experience should decide the operative approach, but it is important to discuss the differences between these approaches with patients.

Background: Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs)., Methods: Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method., Results: Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p < 0.01), while African American (OR 6.87, p = 0.02) and Asian race (OR 3.12, p ≤ 0.01), signet ring cells on biopsy (OR 3.14, p < 0.01), and distal tumors (OR 1.62, p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1)., Conclusions: Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients., (© 2022 Wiley Periodicals LLC.)

Objective: Compare the effectiveness of 1st-3rd generation cephalosporins (1st-3rdCE) to broad-spectrum antibiotics in decreasing surgical site infections (SSI) after pancreatectomy., Summary of Background Data: SSI is one of the most common complications after pancreatic surgery. Various antibiotic regimens are utilized nationwide with no clear guidelines for pancreatectomy. As we await results of a recently initiated prospective trial, this study retrospectively evaluates over 15,000 patients using the same administrative data abstraction tools as in the trial., Methods: All relevant clinical variables were collected from the 2016-2018 targeted-pancreatectomy database from the American College of Surgeon National Surgical Quality Improvement Program. Preoperative antibiotics were initially collected as first-generation cephalosporin, second or third-generation cephalosporin, and broad-spectrum antibiotics (Broad-abx)., Results: Of the 15,182 patients who completed a pancreatic surgery between 2016 and 2018, 6114 (40%) received a first-generation cephalosporin, 4097 (27%) received a second or third-generation cephalosporin, and 4971 (33%) received Broad-abx. On multivariate analysis, Broad-abx was associated with a decrease in all-type SSI compared to 1st-3rdCE (odds ratio = 0.73-0.77, P < 0.001) after open pancreaticoduodenectomy (PD). There was no difference in SSI between antibiotic-types after distal pancreatectomy. Subgroup multivariate analysis of open PD revealed decrease in all-type SSI with Broad-abx amongst patients with jaundice and/or biliary stent only, regardless of wound protector use (odds ratio = 0.69-0.70, P < 0.001). Propensity score matching of open PD patients with jaundice and/or biliary stent confirmed a decrease in all-type SSI (19% vs 24%, P = 0.001), and organ-space SSI (12% vs 16%, P < 0.001)., Conclusion: Broad-abx are associated with decreased SSI after open PD and may be preferred specifically for patients with preoperative biliary stent and/ or jaundice., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Increased tumor infiltrating lymphocytes (TIL) are associated with improved patient responses to immunotherapy. As a result, there is interest in enhancing lymphocyte trafficking particularly to colon cancers since the majority are checkpoint blockade-resistant and microsatellite stable. Here, we demonstrate that activated T-cells (ATC) armed with anti-CD3 x anti-EGFR bispecific antibody increases TIL and mediate anti-tumor cytotoxicity while decreasing tumor cell viability. Furthermore, treatment induces endogenous anti-tumor immunity that resisted tumor rechallenge and increased memory T-cell subsets in the tumor. When combined with targeted tumor expression of the tumor necrosis factor superfamily member LIGHT, activated T-cell proliferation and infiltration were further enhanced, and human colorectal tumor regressions were observed. Our data indicate that tumor-targeted armed bispecific antibody increases TIL trafficking and is a potentially potent strategy that can be paired with combination immunotherapy to battle microsatellite stable colon cancer. SIGNIFICANCE: Enhancing trafficking of tumor infiltrating lymphocytes (TILs) to solid tumors has been shown to improve outcomes. Unfortunately, few strategies have been successful in the clinical setting for solid tumors, particularly for "cold" microsatellite stable colon cancers. In order to address this gap in knowledge, this study combined TNFSF14/LIGHT immunomodulation with a bispecific antibody armed with activated T-cells targeted to the tumor. This unique T-cell trafficking strategy successfully generated anti-tumor immunity in a microsatellite stable colon cancer model, stimulated T-cell infiltration, and holds promise as a combination immunotherapy for treating advanced and metastatic colorectal cancer., (© 2022. The Author(s).)

Biliary tract cancer consists of cholangiocarcinoma (CC) and gallbladder cancer (GBC). When resectable, surgery provides the best chance at long-term survival. Unfortunately, surgery for these tumors is associated with long operative times, high morbidities, and prolonged hospital stays. Minimally invasive surgery has been shown to impact selected outcomes, including length of stay, in other diseases, and robotic surgery may offer additional advantages compared to laparoscopic surgery in treating bile duct cancers. This is a systematic review of robotic surgery for biliary tract cancer. Predetermined selection criteria were used to appraise the literature. The PRISMA guidelines were followed. In total, 20 unique articles with a total of 259 patients with biliary tract cancer undergoing robotic surgery met the inclusion criteria. For CC and GBC, respectively, the weighted average operative time was 401 and 277 min, the estimated blood loss was 348 and 260 mL, the conversion rate to open was 7 and 3.5%, the all-cause morbidity was 52 and 9.7%, the major morbidity was 12 and 4.4%, the perioperative mortality was 1.4 and 0%, the length of stay was 15 and 4.8 days, the positive margin rate was 27 and 9%, and the number of lymph nodes retrieved was 4.2 and 8. Robotic surgery for biliary tract cancer appears non-inferior to open surgery when compared to the published contemporary data. However, the current literature on the topic is of low quality, and future prospective/randomized studies are needed.

Background: Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population., Methods: Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS)., Results: Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS., Conclusions: A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population., (Copyright © 2021. Published by Elsevier Inc.)

Background: Neoadjuvant chemotherapy (NAC) is standard management for localized gastric cancer (GC). Attrition during NAC due to treatment-related toxicity or functional decline is considered a surrogate for worse biologic outcomes; however, data supporting this paradigm are lacking. We investigated factors predicting attrition and its association with overall survival (OS) in GC., Methods: Patients with nonmetastatic GC initiating NAC were identified from the US Safety-Net Collaborative (2012-2014). Patient/treatment-related characteristics were compared between attrition/nonattrition cohorts. Cox models determined factors associated with OS., Results: Of 116 patients initiating NAC, attrition during prescribed NAC occurred in 24%. No differences were observed in performance status, comorbidities, treatment at safety-net hospital, or clinicopathologic factors between cohorts. Despite absence of distinguishing factors, attrition was associated with worse OS (median: 11 vs. 37 months; p = 0.01) and was an independent predictor of mortality (hazard ratio [HR]: 4.7, 95% confidence interval [CI]: 1.5-15.2; p = 0.02). Fewer patients with attrition underwent curative-intent surgery (39% vs. 89%; p < 0.001). Even in patients undergoing surgical exploration (n = 89), NAC attrition remained an independent predictor of worse OS (HR: 50.8, 95% CI: 3.6-717.8; p = 0.004) despite similar receipt of adjuvant chemotherapy., Conclusion: Attrition during NAC for nonmetastatic GC is independently associated with worse OS, even in patients undergoing surgery. Attrition during NAC may reflect unfavorable tumor biology not captured by conventional staging metrics., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: Perioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC)., Materials and Methods: Patients in the US Safety Net Collaborative (2012-2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy., Results: Of 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p < 0.05) while treatment facility type was not., Conclusions: There was no difference in utilization of a perioperative treatment strategy between facility types for patients with gastric cancer. Pathologic downstaging from NAC was similar across treatment facilities, suggesting similar quality and duration of therapy. Treatment at an SNH is not a barrier to receiving standard-of-care perioperative therapy for gastric cancer., (© 2021 Wiley Periodicals LLC.)

Background: The impact of epidural analgesia (EA) on postoperative morbidity and length of stay (LOS) after HPB surgery remains to be determined. These specific outcomes have been highlighted by the implementation of multiple enhanced recovery pathways (ERAS). The authors hypothesized that EA in the current environment may be associated with LOS and other outcomes., Methods: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases from 2014 to 2017 for patients undergoing open hepatopancreaticobiliary (HPB) surgery were included in a retrospective cohort analysis with propensity score matching (PSM) comparing EA with control., Results: Twenty-seven thousand two hundred eighteen patients underwent open HPB surgery, of which 6048 (22%) received EA. There was an increase use of EA over time (from 19.3 to 25.5%, p = 0.001). On PSM, EA was associated with more than half of a day increase in LOS for both pancreatic (p < 0.001) and hepatic surgery (p < 0.001). Furthermore, for pancreatic surgery, there was an increase in urinary tract infection (2.5% vs. 3.3%, p = 0.018), time to drain removal (7.8 vs. 8.7 days, p < 0.001), and discharge to rehabilitation (2.9% vs. 4.3%, p = 0.029). For hepatic surgery, there was an increase in blood transfusion requirements (17% vs. 20%, p = 0.019). There were no differences in overall morbidity and mortality., Conclusion: In this cohort of over 27,000 patients with granular surgical details, there was a significant increase in LOS associated with EA after HPB surgery, along with increased procedure-specific UTI and blood transfusion. With the ever-increasing need for standardized and efficient patient care pathways that reduce LOS, alternative analgesic adjuncts may be considered to optimize patient outcomes., (© 2020. The Society for Surgery of the Alimentary Tract.)

Background: The generation of long-term durable tumor immunity and prolonged disease-free survival depends on the ability to generate and support CD8+ central memory T-cells. Microsatellite-stable colon cancer is resistant to currently available immunotherapies; thus, development of novel mechanisms to increase both lymphocyte infiltration and central memory formation are needed to improve outcomes in these patients. We have previously demonstrated that both interleukin-2 (IL-2) and LIGHT (TNFSF14) independently enhance antitumor immune responses and hypothesize that combination immunotherapy may increase the CD8+ central memory T-cell response., Methods: Murine colorectal cancer tumors were established in syngeneic mice. Tumors were treated with control, soluble, or liposomal IL-2 at established intervals. A subset of animal tumors overexpressed tumor necrosis superfamily factor LIGHT (TNFSF14). Peripheral blood, splenic, and tumor-infiltrating lymphocytes were isolated for phenotypic studies and flow cytometry., Results: Tumors exposed to a combination of LIGHT and IL-2 experienced a decrease in tumor size compared with IL-2 alone that was not demonstrated in wild-type tumors or between other treatment groups. Combination exposure also increased splenic central memory CD8+ cells compared with IL-2 administration alone, while not increasing tumor-infiltrating lymphocytes. In the periphery, the combination enhanced levels of circulating CD8 T-cells and central memory T-cells, while also increasing circulating T-regulatory cells., Conclusions: Combination of IL-2, whether soluble or liposomal, with exposure to LIGHT results in increased CD8+ central memory cells in the spleen and periphery. New combination immunotherapy strategies that support both effector and memory T-cell functions are critical to enhancing durable antitumor responses and warrant further investigation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Immunotherapy has changed the environment of cancer treatment by providing new and efficacious therapy options for many solid and hematologic malignancies. Although not a new field of oncology, immunotherapy has quickly developed into one of the most flourishing fields in medicine. In this review article, we explore key discoveries which helped to shape our current understanding of the immune system's role in neoplasms. Many landmark developments include the advancements in checkpoint inhibitors, monoclonal antibodies, CAR-T cells and anti-cancer vaccines. We also explore the drawbacks and efficacy of various categories of immunotherapy. Ongoing investigations within immunotherapy, such as the gut microbiome, combining checkpoint inhibitors and gene sequencing, continue to personalize treatments for cancer patients, providing exciting and endless possibilities for the future.

The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

The management of symptomatic giant hepatic hemangiomas (> 10 cm) varies in the literature. Multiple interventional approaches have been described including surveillance, embolization, enucleation, and resection based on tumor size, location, relationship to vascular and biliary structures, and the quality and quantity of the functional liver remnant. Resection is often performed as a last resort due to the risk of major hemorrhage. Preoperative arterial embolization is an option; however, many patients will experience severe pain, fever, transaminitis, acidosis, recanalization, and collateral inflow that limit its utility. Furthermore, patients require post-procedure inpatient observation, and there is no consensus on the appropriate time interval between procedures. We present and demonstrate a technique in the video that utilizes a hybrid operating room with on-table angiogram capabilities to perform hemangioma inflow embolization and immediate hepatic resection under the same anesthesia in a single procedure. Combining on-table embolization with immediate resection avoids many of the pitfalls of preoperative embolization, while enhancing the safety of the resection by decreasing the size of the tumor, enabling compressibility, and facilitating exposure of the vascular inflow and outflow. It is an efficient use of hospital resources and eliminates an intervening hospital admission. We have found it to be a preferred approach to enhance the safety and feasibility of resection for massive hepatic hemangiomas with minimal intraoperative blood loss and reduced risk.

Background: Post-operative pancreatic fistula (POPF) remains one of the most common complications after pancreatic surgery. We previously reported that the majority of US surgeons leave drains after pancreatectomy. However, there remains controversy and surgeon bias on the use of gravity compared with suction drainage with limited data on patient outcomes to guide management., Methods: Demographics, comorbidities, perioperative, and outcome data were captured from the most recent ACS National Surgical Quality Improvement Program (NSQIP)-targeted pancreatectomy databases. This is a retrospective cohort analysis comparing closed-suction to closed-gravity drains with multivariate analysis and propensity score matching (PSM)., Results: Of 9232 patients that underwent a pancreatectomy with closed drain placement, 1345 (15%) were to gravity and 7887 (85%) were to suction. On multivariate and PSM, stratified by surgery-type, there was no difference in biochemical leak (Whipple, 4 vs. 4%; distal, 8 vs. 6%) or clinically relevant (CR)-POPF (Whipple, 13 vs. 15%; distal, 12 vs. 15%). On multivariate analysis, there was an increase in organ-space surgical site infections with suction drains for patients undergoing Whipple procedure (12 vs. 16%, p = 0.004), which did not persist on PSM (p = 0.088). Finally, there were no significant differences in amylase level, time to drain removal, or superficial surgical site infections for patients undergoing either procedure based on drain type., Conclusion: The majority of drains utilized after pancreatectomy in the USA are placed to suction, though a significant proportion are kept to gravity. Neither type of drain is associated with increased CR-POPF or other post-operative outcomes compared with the other; therefore, both types remain reasonable options if drains are to be placed.

Background: Pancreatectomy results in significant postoperative pain and typically requires opioid analgesia for adequate pain control. Local anesthetics may decrease postoperative pain and opioid requirements but can be limited by onset of action, duration of effect, and inability to titrate dosing after administration. This can be overcome by surgeon placement of tunneled peri-incisional catheters with continuous wound infusion (CWI)., Methods: This retrospective cohort study analyzed patients undergoing open pancreatic tumor resection. All the patients received patient-controlled analgesia (PCA), enabling an objective comparison of opioid requirements, and underwent the same recovery pathway. The patients received CWI (n = 45), PCA alone (n = 11), or epidural analgesia (EA) (n = 9). The primary outcome was total opioid use in terms of intravenous morphine milligram equivalents (MMEs) and patient-reported pain scores on a numeric rating scale (NRS) of 0 to 10., Results: No differences in baseline patient or tumor characteristics were observed. In both the uni- and multivariate analyses, CWI was associated with lower opioid use than PCA (MME, 83 vs 207 mg; p = 0.004) or EA (MME, 83 vs 156 mg; p < 0.001) without having a negative impact on pain scores. Furthermore, CWI was associated with a greater percentage of time that patients experienced optimal pain control (NRS, ≤ 4: 63% vs 50%; p = 0.033) and a shorter time to PCA independence (4.0 vs 4.9 days; p = 0.004) than PCA alone. In addition, CWI was associated with earlier ambulation [EA vs CWI: odds ratio (OR), 0.05; p = 0.021], improved spirometry performance (CWI vs PCA: regression coefficient (coef), 267; p = 0.013), and earlier urinary catheter removal (EA vs CWI: coef, 1.30; p = 0.013). The findings showed no differences in time to return of bowel function, antiemetic use, or hospital length of stay., Conclusions: After open pancreatic tumor resection, CWI is safe and associated with decreased opioid requirements and improved functional outcomes without a negative impact on pain scores, supporting its potential for preferred use over PCA or EA alone.

LIGHT, also known as tumor-necrosis factor (TNF) superfamily member 14 (TNFSF14), is predominantly expressed on activated immune cells and some tumor cells. LIGHT is a pivotal regulator both for recruiting and activating immune cells in the tumor lesions. In this study, we armed human telomerase reverse transcriptase (TERT) promoter controlled oncolytic adenovirus with LIGHT to generate rAd.Light. rAd.Light effectively transduced both human and mouse breast tumor cell lines in vitro, and expressed LIGHT protein on the surface of tumor cells. Both rAd.Null, and rAd.Light could replicate in human breast cancer cells, and produced cytotoxicity to human and mouse mammary tumor cells. rAd.Light induced apoptosis resulting in tumor cell death. Using a subcutaneous model of 4T1 cells in BALB/c mice, rAd.Light was delivered intratumorally to evaluate the anti-tumor responses. Both rAd.Light and rAd.Null significantly inhibited the tumor growth, but rAd.Light produced much stronger anti-tumor effects. Histopathological analysis showed the infiltration of T lymphocytes in the tumor tissues. rAd.Light also induced stronger cellular apoptosis than rAd.Null in the tumors. Interestingly, on day 15, compared to rAd.Null, there was a significant reduction of Tregs following rAd.Light treatment. rAd.Light significantly increased Th1 cytokine interleukin (IL)-2 expression, and reduced Th2 cytokines expression, such as transforming growth factor β (TGF-β) and IL-10 in the tumors. These results suggest rAd.Light induced activation of anti-tumor immune responses. In conclusion, rAd.Light produced anti-tumor effect in a subcutaneous model of breast cancer via inducing tumor apoptosis and evoking strong anti-tumor immune responses. Therefore, rAd.Light has great promise to be developed as an effective therapeutic approach for the treatment of breast cancer.

Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major cause of morbidity in patients undergoing pancreatic surgery. Controversy exists as to whether there is any difference in CR-POPF with a Duct-to-Mucosa (DTM) versus an Invagination (IG) pancreaticojejunostomy (PJ)., Methods: Demographic, perioperative, intraoperative, and postoperative data were captured from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2014-2017 databases. Potential confounders were included in a logistic regression and a propensity score model. The primary outcome was CR-POPF., Results: A total of 12,361 pancreaticojejunal anastomoses were performed with 11,168 patients undergoing DTM (90%) and 1193 undergoing IG (10%) after pancreaticoduodenectomy. Amongst all patients, there was no significant difference in CR-POPF between DTM and IG on multivariate (OR = 0.95, p = 0.64) or propensity score analysis (OR = 0.99, p = 0.93). After stratification by pancreatic gland texture and duct size, there was a decrease in CR-POPF with DTM amongst patients with duct size greater than 6 mm on multivariate analysis (OR = 0.35, p = 0.009) and propensity score analysis (OR = 0.40, p = 0.018). There were no significant differences in any other strata., Conclusion: DTM or IG technique are not associated with CR-POPF for patients with average size pancreatic ducts; however, DTM is preferable in patients with large pancreatic duct diameter (>6 mm)., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Anaplastic Thyroid Cancer (ATC) accounts for >40% thyroid cancer-related deaths and has a dismal prognosis. In the past decade, significant efforts have been made towards understanding the pathogenesis of this disease and developing novel therapeutics. Unfortunately, effective treatment is still lacking and a more thorough understanding of ATC pathogenesis may provide new opportunities to improve ATC therapeutics. This review provides insights into ATC clinical presentation and pathology, and the putative role of genetic aberrations and alterations in molecular signaling pathways in ATC pathogenesis. We reviewed prevalent mutations, chromosomal abnormalities and fusions, epigenetic alterations and dysregulations in ATC, and highlighted several signaling cascades which appeared to be integral to ATC pathogenesis. Moreover, these features offer insights into de-differentiated, aggressive and drug-resistant phenotype of ATC, and thus may help in exploring potential new molecular targets for developing novel therapeutics., (Published by Elsevier B.V.)

Background: Adjuvant immunotherapy has improved outcomes in patients with advanced melanoma; however, the potential benefit for patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was to determine the impact of adjuvant chemotherapy and immunotherapy (CTx-IT) compared with CTx alone on patient survival after resection of PDAC., Study Design: Patients who underwent resection of PDAC from 2004 to 2015 were identified from the National Cancer Database. Univariate and multivariate Cox proportional hazards models were used to determine predictors of overall survival (OS) based on the type of adjuvant therapy received. Patients who received adjuvant immunotherapy were compared with those who received adjuvant CTx alone by propensity score matching., Results: Of 21,313 patients who received curative-intent resection for PDAC followed by adjuvant systemic therapy, 269 (1.3%) patients were treated with adjuvant CTx-IT. Propensity score matching resulted in a cohort of 477 patients: (229 CTx only and 248 CTx-IT). The 5-year OS was higher in the CTx-IT group compared with CTx alone (29.2% vs 18.3%; p = 0.0045). On multivariate analysis, the addition of adjuvant immunotherapy was associated was improved overall survival (hazard ratio 0.74; p = 0.007)., Conclusions: The addition of adjuvant immunotherapy to chemotherapy is associated with improved survival compared with chemotherapy alone after curative-intent resection of pancreatic adenocarcinoma. Future research is warranted to match specific immunotherapy agents with susceptible patient populations to improve outcomes for this aggressive disease., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)