CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival.

Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type. In the context of pancreatic cancer, we have previously reported that CD200 is expressed in the pancreatic tumor microenvironment (TME), and that targeting CD200 in murine tumor models reduces tumor burden. We hypothesized that CD200 is overexpressed on tumor and stromal populations in the pancreatic TME and that circulating levels of soluble CD200 (sCD200) have prognostic value for overall survival. We discovered that CD200 was overexpressed on immune, stromal, and tumor populations in the pancreatic TME. Particularly, single-cell RNA-sequencing indicated that CD200 was upregulated on inflammatory cancer-associated fibroblasts. Cytometry by time of flight analysis of PBMCs indicated that CD200 was overexpressed on innate immune populations, including monocytes, dendritic cells, and monocytic myeloid-derived suppressor cells. High sCD200 levels in plasma correlated with significantly worse overall and progression-free survival. Additionally, sCD200 correlated with the ratio of circulating matrix metalloproteinase (MMP) 3: tissue inhibitor of metalloproteinase (TIMP) 3 and MMP11/TIMP3. This study highlights the importance of CD200 expression in pancreatic cancer and provides the rationale for designing novel therapeutic strategies that target this protein.

The Influence of Intraoperative Blood Loss on Fistula Development Following Pancreatoduodenectomy.

OBJECTIVE: To investigate the role of intraoperative estimated blood loss (EBL) on development of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). BACKGROUND: Minimizing EBL has been shown to decrease transfusions and provide better perioperative outcomes in PD. EBL is also felt to be influential on CR-POPF development. METHODS: This study consists of 5534 PDs from a 17-institution collaborative (2003-2018). EBL was progressively categorized (≤150mL; 151-400mL; 401-1,000 mL; > 1,000 mL). Impact of additive EBL was assessed using 20 3- factor fistula risk score (FRS) scenarios reflective of endogenous CR-POPF risk. RESULTS: CR-POPF developed in 13.6% of patients (N = 753) and median EBL was 400 mL (interquartile range 250-600 mL). CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs 400 mL, P = 0.002; 372 vs 500 mL, P < 0.001, respectively). Progressive EBL cohorts displayed incremental CR-POPF rates (8.5%, 13.4%, 15.2%, 16.9%; P < 0.001). EBL >400mL was associated with increased CR-POPF occurrence in 13/20 endogenous risk scenarios. Moreover, 8 of 10 scenarios predicated on a soft gland demonstrated increased CR-POPF incidence. Hypothetical projections demonstrate significant reductions in CR-POPF can be obtained with 1-, 2-, and 3-point decreases in FRS points attributed to EBL risk (12.2%, 17.4%, and 20.0%; P < 0.001). This is especially pronounced in high-risk (FRS7-10) patients, who demonstrate up to a 31% reduction (P < 0.001). Surgeons in the lowest-quartile of median EBL demonstrated CR-POPF rates less than half those in the upper-quartile (7.9% vs 18.8%; P < 0.001). CONCLUSION: EBL independently contributes significant biological risk to CR-POPF. Substantial reductions in CR-POPF occurrence are projected and obtainable by minimizing EBL. Decreased individual surgeon EBL is associated with improvements in CR-POPF.

The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. BACKGROUND: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. METHODS: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches. RESULTS: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). CONCLUSION: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer.

The neonatal Fc receptor (FcRn) is responsible for recycling of IgG antibodies and albumin throughout the body. This mechanism has been exploited for pharmaceutic delivery across an array of diseases to either enhance or diminish this function. Monoclonal antibodies and albumin-bound nanoparticles are examples of FcRn-dependent anti-cancer therapeutics. Despite its importance in drug delivery, little is known about FcRn expression in circulating immune cells. Through time-of-flight mass cytometry (CyTOF) we were able to characterize FcRn expression in peripheral blood mononuclear cell (PBMC) populations of pancreatic ductal adenocarcinoma (PDAC) patients and non-cancer donors. Furthermore, we were able to replicate these findings in an orthotopic murine model of PDAC. Altogether, we found that in both patients and mice with PDAC, FcRn was elevated in migratory and resident classical dendritic cell type 2 (cDC2) as well as monocytic and granulocytic myeloid-derived suppressor cell (MDSC) populations compared to tumor-free controls. Furthermore, PBMCs from PDAC patients had elevated monocyte, dendritic cells and MDSCs relative to non-cancer donor PBMCs. Future investigations into FcRn activity may further elucidate possible mechanisms of poor efficacy of antibody immunotherapies in patients with PDAC.

Women in hepatopancreaticobiliary surgery: is there a pipeline problem?

BACKGROUND: Women are underrepresented in hepatopancreatobiliary (HPB) surgery. We investigated whether this is a pipeline problem by looking at the percentage of women trainees presenting at Americas Hepato-Pancreato-Biliary Association (AHPBA) and then determining their ultimate career path. METHODS: We extracted gender, level of training, and career path of first authors of abstracts presented at the 2007 and 2012 AHPBA conferences. Chi-square analysis and Fisher's exact test were used to examine gender trends. RESULTS: 85 authors in 2007 and 109 in 2012 met inclusion criteria. 16.5% of presenters were female in 2007 compared to 22.9% in 2012. Just over 50% of authors went into academic medicine in 2007 (55%) and 2012 (59%) which did not differ by gender (p = 0.868 in 2007, p = 0.174 in 2012). 41.2% of first authors from 2007 to 2012 went into an HPB related field which did not differ significantly by gender (p = 0.450 for 2007, p = 0.626 for 2012). CONCLUSION: Similar percentages of men and women who present at AHPBA ultimately obtain an HPB related job, however, more men than women trainees present at AHPBA. More efforts to encourage women to go into HPB surgery early may help eliminate this gender gap.

Wide variation in inpatient opioid utilization following hepatopancreatic surgery.

BACKGROUND: Inpatient opioid utilization following major surgery remains relatively unknown. We sought to characterize inpatient opioid consumption following hepatopancreatic surgery and determine factors associated with the variability in opioid utilization. METHODS: Adult patients who underwent hepatopancreatic surgery at a single institution were identified. Multimodal pain management strategies assessed included opioids (oral morphine equivalents, OME), acetaminophen, ibuprofen and ketorolac. RESULTS: Among 2,054 patients, the median total OME utilized was 465 (129-815) during a patient's hospitalization following hepatopancreatic surgery. The interquartile range for total OMEs administered following hepatopancreatic surgery was as high as 940 OMEs (125 oxycodone-5mg pills) following a pancreaticoduodenectomy versus 520 OMEs (69 oxycodone-5mg pills) following a hemi-hepatectomy. Despite relatively high use of acetaminophen post-operatively (n = 1,588, 77.0%), multimodal pain control with acetaminophen and ibuprofen was infrequent (n = 175, 8.5%). Furthermore, individuals with high opioid utilization used on average 147 OMEs (20 oxycodone-5mg pills) the day before discharge versus 44 OME (6 oxycodone-5mg pills) among patients with expected opioid utilization. CONCLUSIONS: Marked variability in inpatient opioid consumption following hepatopancreatic surgery was noted. Future work is necessary to decrease the variability in inpatient opioid prescribing practices to promote the safe and effective management of pain.

Association of pre-existing mental illness with all-cause and cancer-specific mortality among Medicare beneficiaries with pancreatic cancer.

BACKGROUND: Among patients with pancreatic cancer, the association of pre-existing mental illness with long-term outcomes remains unknown. METHODS: Individuals diagnosed with pancreatic adenocarcinoma were identified in the SEER-Medicare database. Patients were classified as having mental illness if an ICD9/10CM code for anxiety, depression, bipolar disorder, schizophrenia or other psychotic disorder was recorded. RESULTS: Among the 54,234 Medicare beneficiaries with pancreatic cancer, roughly 1 in 12 (n = 4793, 8.83%) individuals had a diagnosis of a mental illness. The majority (n = 4029, 84.1%) had anxiety or depression, while 16% (n = 764) had bipolar/schizophrenic disorders. On multivariable analysis, among patients with early stage cancer, individuals with pre-existing anxiety/depression and bipolar/schizophrenic disorders had 22% (OR 0.78, 95% CI 0.69-0.86) and 46% (OR 0.54, 95% CI 0.42-0.70) reduced odds, respectively, to undergo cancer-directed surgery. Furthermore, patients with a pre-existing history of bipolar/schizophrenic disorders had a 20% (HR 1.20, 95% CI 1.21-1.40) higher risk of all-cause mortality and 27% (HR 1.27, 95% CI 1.17-1.37) higher risk of pancreatic cancer-specific mortality compared to individuals without a history of mental illness. CONCLUSION: One in twelve patients with pancreatic cancer had a pre-existing mental illness. Individuals with mental illness were more likely to have worse overall and cancer-specific long-term outcomes.

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions.

BACKGROUND & AIMS: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. METHODS: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. RESULTS: The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. CONCLUSIONS: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Travel to a high volume hospital to undergo resection of gallbladder cancer: does it impact quality of care and long-term outcomes?

BACKGROUND: The relationship of volume and travel distance to patient outcomes after resection of gallbladder cancer (GBC) remains poorly defined. METHODS: The 2004-2015 National Cancer Database was used to identify GBC resection patients and examine the impact of travel distance, hospital volume and both on overall survival (OS) and quality of care indicators. RESULTS: Among 10,174 patients undergoing surgery for GBC, the majority of patients were Caucasian (N = 8,175, 80%) and had a Charlson-Deyo comorbidity score of 0 (N = 6,785, 67%). On unadjusted survival analysis increasing travel distance and hospital volume were associated with improved OS (both p < 0.001). After controlling for competing risk factors, the 4th quartile of hospital volume was associated with a decreased hazard of death (HR 0.831, 95% CI 0.751-0.920, p < 0.001). When both hospital volume and travel distance were included, the association with improved OS persisted only for hospital volume (4th quartile HR 0.835, 95% CI 0.753-0.925, p < 0.001), whereas there was no independent association of increasing travel distance with OS. CONCLUSIONS: Both increasing travel distance and hospital volume were associated with improved OS; however, adjusted models demonstrated that the impact of travel distance was mediated through hospital volume.

Predictors of Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Risk factors for hospital readmission after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are poorly understood. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program databases from 2011 to 2016 were used to identify all patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative variables were examined using logistic regression to identify factors associated with 30-d postoperative readmission. RESULTS: Among 618 patients who underwent CRS-HIPEC, 96 (15.5%) required hospital readmission within 30 d of surgery. The incidence of readmission decreased over the study period (18.3% in 2011 to 4.8% in 2016). Among the 59 patients who were readmitted and had complete data available, readmission occurred on mean postoperative day 18.5 ± 5.5; the most common reasons for readmission were digestive complications (39.0%), postoperative infections (25.4%), uncontrolled pain (8.5%), and venous thromboembolism (5.1%). On multivariate logistic regression analysis, increasing age (OR 1.02, 95% CI 1.00-1.05), number of operative procedures (OR 1.12, 95% CI 1.00-1.25), perioperative complication (OR 7.06, 95% CI 3.96-12.59), need for reoperation (OR 10.21, 95% CI 3.50-29.83), and length of stay (OR 0.93, 0.90-0.97) were associated with hospital readmission. CONCLUSIONS: In this population-based analysis of patients undergoing CRS-HIPEC, older age, perioperative complications, need for reoperation, and extent of cytoreduction were associated with hospital readmission. The American College of Surgeons-National Surgical Quality Improvement Program database is a powerful research tool that can be used to identify opportunities to improve the perioperative care of surgical patients.

Perioperative Morbidity of Gastrectomy During CRS-HIPEC: An ACS-NSQIP Analysis.

BACKGROUND: Formal gastrectomy is occasionally required to achieve complete cytoreduction for patients with peritoneal surface malignancies. In addition, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer is increasingly being explored. Nevertheless, data on the safety of gastrectomy at the time of CRS-HIPEC are limited. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program databases from 2005 to 2016 were used to identify patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative outcomes were compared between patients who underwent CRS-HIPEC with and without gastrectomy. RESULTS: Among 1168 patients who underwent CRS-HIPEC, 43 (4%) underwent partial (n = 20) or total (n = 23) gastrectomy. Patients who underwent gastrectomy at the time of CRS-HIPEC had a longer operative time (529.3 versus 457.6 min, P = 0.004), were more likely to need an intraoperative transfusion (32.6% versus 14.3%, P = 0.001), experienced a longer length of stay (19.0 versus 11.3 d, P < 0.001), and had a significantly greater complication rate (60.5% versus 27.9%, P < 0.001), whereas postoperative mortality was not statistically significantly different (4.7% versus 1.4%, P = 0.09). On multivariate logistic regression, gastrectomy (odds ratio [OR] 3.52, P < 0.001) was the strongest predictor of postoperative morbidity, in addition to American Society of Anesthesiologists class 4 (OR 2.82, P = 0.001), malnutrition (OR 1.63, P = 0.01), liver resection (OR 1.88, P = 0.01), and colectomy (OR 2.04, P < 0.001). CONCLUSIONS: Patients undergoing gastrectomy at the time of CRS-HIPEC experience a substantial postoperative complication rate (60%) and extended length of stay (mean 19 d). These findings highlight the need for cautious patient selection and preoperative counseling before performing concomitant gastrectomy and CRS-HIPEC.

Hospice utilization among Medicare beneficiaries dying from pancreatic cancer.

BACKGROUND: Use of hospice services among patients with pancreatic cancer following pancreatic resection remains unknown. METHODS: Patients with pancreatic cancer who underwent resection were identified in the Medicare Standard Analytic Files. Outcomes included overall hospice use, early hospice enrollment (≥4 weeks before death), late hospice enrollment (initiation within 3 days of death), and Medicare expenditures. RESULTS: Among the 4369 deceased individuals, three-fourths of patients (n = 3252, 74.4%) used hospice at the time of death. Patients who did not use hospice were more likely to be male, have a complication on index admission and receive life sustaining treatments on subsequent admissions (P < .05). Only one-third (32.2%) of patients initiated hospice services early. Medicare expenditure during the last month of life was $10 000 lower among patients who initialized hospice services at least 1 month before death versus within 3 days of death (late: $10 581 [$5454-$17 200], early: $221 [$46-$733]; P < .001) CONCLUSION: While three-fourths of patients utilized hospice services after pancreatic resection, only one-third of patients initiated hospice services at least one-month before death. Late hospice use was associated with higher Medicare expenditures during the last month of life. Further research is needed to understand barriers to early hospice utilization.

Sequential drain amylase to guide drain removal following pancreatectomy.

BACKGROUND: Although used as criterion for early drain removal, postoperative day (POD) 1 drain fluid amylase (DFA) ≤ 5000 U/L has low negative predictive value for clinically relevant postoperative pancreatic fistula (CR-POPF). It was hypothesized that POD3 DFA ≤ 350 could provide further information to guide early drain removal. METHODS: Data from a pancreas surgery consortium database for pancreatoduodenectomy and distal pancreatectomy patients were analyzed retrospectively. Those patients without drains or POD 1 and 3 DFA data were excluded. Patients with POD1 DFA ≤ 5000 were divided into groups based on POD3 DFA: Group A (≤350) and Group B (>350). Operative characteristics and 60-day outcomes were compared using chi-square test. RESULTS: Among 687 patients in the database, all data were available for 380. Fifty-five (14.5%) had a POD1 DFA > 5000. Among 325 with POD1 DFA ≤ 5000, 254 (78.2%) were in Group A and 71 (21.8%) in Group B. Complications (35 (49.3%) vs 87 (34.4%); p = 0.021) and CR-POPF (13 (18.3%) vs 10 (3.9%); p < 0.001) were more frequent in Group B. CONCLUSIONS: In patients with POD1 DFA ≤ 5000, POD3 DFA ≤ 350 may be a practical test to guide safe early drain removal. Further prospective testing may be useful.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage.

OBJECTIVE: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos).

BACKGROUND AND AIMS: EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. METHODS: Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. RESULTS: A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. CONCLUSIONS: EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).

Minimally Invasive Techniques for Gastrectomy.

Gastric adenocarcinoma is an aggressive disease and a leading cause of cancer-related deaths worldwide. Surgery entails either a total or a subtotal gastrectomy. These complex operations carry elevated morbidity and mortality with an extended recovery time. As such, research has focused on minimizing these risks and enhancing postoperative care. Robotic surgery is a newer platform that helps overcome some of the limitations of laparoscopy through three-dimensional vision, better mobility, and improved surgeon dexterity. As such, many surgeons have embraced robotics and advocated for their implementation in cancer surgery. This review will discuss the technical considerations of performing a robotic gastrectomy.

Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer-induced cachexia.

Background: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes. Methods: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia. Results: Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males. Conclusions: Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.

A risk-adjusted analysis of drain use in pancreaticoduodenectomy: Some is good, but more may not be better.

BACKGROUND: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. METHODS: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. RESULTS: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. CONCLUSION: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Using Endoscopic Optical Coherence Tomography to Detect and Treat Early-Stage Pancreatic Cancers.

We developed a novel technology capable of detecting early-stage pancreatic cancers using high-resolution three-dimensional endoscopic optical coherence tomography (Endo-OCT), and treating them using high dose rate brachytherapy (HDR) under the Endo-OCT image guidance. This technology integrates our custom-built ultra-high resolution endoscopic three-dimensional OCT diagnostic imaging device with a commercial high dose rate brachytherapy system (HDR), resulting in a compact, portable, easy-to-operate, and low-cost Endo-OCT image-guided high dose rate brachytherapy (OCT-IGHDR) system. The system has the dual functions of diagnosis and treatment that can precisely detect and measure the location and size of the early-stage pancreatic cancer or premalignant lesions and then treat them from the inside of the pancreatic duct with an accurate and focused dose while greatly reducing the radiation toxicity to the neighboring tissues and organs. This minimally-invasive treatment technology could avoid the potential complications from surgery and reduces the high operation cost. This technology could also be applied to treat diseases of the esophagus, rectum, bronchus, and other aerodigestive organs that are suitable for use with an endoscopic device. In this article, we describe the concept of this technology and the preliminary experiments that could demonstrate the concept by using this homemade Endo-OCT machine to image the pancreatic duct for diagnosis of early-stage pancreatic cancer or premalignant lesions and to perform Endo-OCT image-guided brachytherapy.