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Intraductal papillary mucinous neoplasms ( IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis ( CP), IPMN, or pancreatic carcinoma ( PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 ± 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 ± 0.16 for correctly classified lesions and 0.47 ± 0.10 for incorrectly classified lesions ( P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Context: Many patients with unresectable pancreatic and peripancreatic cancer require treatment for malignant biliary obstruction. Objectives: To conduct a meta-analysis of the English language literature (1985–2011) comparing immediate biliary stent placement and immediate surgical biliary bypass in patients with unresectable pancreatic and peripancreatic cancer and analyze associated hospital utilization patterns. Methods: After identifying five randomized controlled trials comparing immediate biliary stent placement and immediate surgical biliary bypass, we performed a meta-analysis for dichotomous outcomes, using a random effects model. We compared resource utilization in terms of the number of hospital days before death by reviewing high-quality literature. Results: Three hundred seventy-nine patients were identified. We found no statistically significant differences in success rates between the two treatments (risk ratio [RR] 0.99; 95% CI 0.93–1.05; P = 0.67). Major complications and mortality were not significantly higher after surgical bypass (RR 1.54; 95% CI 0.87–2.71; P = 0.14). Recurrent biliary obstruction was significantly less frequent after surgical bypass than after stent placement (RR 0.14; 95% CI 0.03–0.63; P < 0.01). Despite similar overall survival rates, longer survival was associated with more hospital days before death in stent patients than in surgical patients. Conclusion: Nearly all patients with unresectable pancreatic cancer benefit from some procedure to manage biliary obstruction. Patients with low surgical risk benefit more from surgery because the risk of recurrence and subsequent hospital utilization are lower than after stent placement. [Copyright &y& Elsevier]

There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits ( n == 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment ( p == 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy. [ABSTRACT FROM AUTHOR]

Background: Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases. Methods: Patients (n = 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival. Results: The median age was 56.8 years (range 11.5-80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3-56.8, P = 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P ~ 0.8). Discussion: Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival. [ABSTRACT FROM AUTHOR]

The article discusses a study investigated the effect of radiofrequency field exposure after targeted nanoparticle treatment in a coculture of two human cancer cell lines that have differential epidermal growth factor receptor (EGFR)-1 expression. The study found that Panc-1 or Cama-1 cells not containing gold nanoparticles or quantum dots had a viability of greater than 92 percent. It showed the biofunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment.

Abstract: Despite the use of hyperthermia to treat cancer for thousands of years, the challenge of only heating malignant cells remains daunting. In pre-clinical and early clinical trials, metal nanoparticles induce hyperthermic cytotoxicity when exposed to near-infrared radiation or radiofrequency fields. We discuss the emerging roles of nanoparticles, especially gold, in the hyperthermic treatment of cancer. In addition, we discuss the similarities of radiofrequency ablation and nanoparticle mediated cytotoxicity. [Copyright &y& Elsevier]

A potential problem during endovascular aortic aneurysm repair (EVAR) or open repair in renal allograft patients is ischemia of the transplanted kidney. In this study, kidney transplant patients who underwent aortic aneurysm repair in our institution were added to similar cases extracted from the literature to represent the basis of this work. Comparisons between patients treated with open surgery versus EVAR were performed in terms of renal function. In the EVAR group, most aneurysms were infrarenal, and 84% were treated with modular bifurcated devices. Protective kidney allograft perfusion measures were not used. The pre- and postoperative Cr was 1.69 and 1.73 mg/dL, respectively (P = .412). All EVAR patients had good outcomes. Complications included 8 endoleaks and 1 limb ischemia case. Three patients died from aortic repair-unrelated reasons. In the open group, the preand postoperative Cr was 1.45 and 1.37 mg/dL, respectively (P = .055). Most cases were infrarenal and mostly treated by aortobiiliac bypasses. In 16%, no adjuvant allograft perfusion was provided. In the rest, temporary axillofemoral bypasses were used most often. Most outcomes were favorable (57%). Reported procedural-related complications included arterial embolism, wound infection, and pneumonia. Deaths were reported in 5 occasions (none allograft failure dependent). No differences in Cr between EVAR and open techniques (P = .13) were seen. Aneurysm repair in kidney transplant recipients is associated with excellent renal preservation. Adverse outcomes were all allograft failure independent in both groups. EVAR without special allograft protection measures seems to be equally effective as open surgery with or without adjuvant kidney transplant perfusion. [ABSTRACT FROM AUTHOR]

Data regarding oncologic outcomes of segmental bile duct resection (SBDR) versus pancreatoduodenectomy (PD) for bile duct cancers (BDC) are conflicting. We compared SBDR and PD for BDC utilizing pooled data analysis. A comprehensive PRISMA 2020 systematic review was performed. Studies comparing SBDR with PD for BDC were included. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Subgroup analyses were performed. Study quality, bias, heterogeneity, and certainty were analyzed. Twelve studies from 2004 to 2021 were included, comprising 533 SBDR and 1,313 PD. SBDR was associated with positive proximal duct margins (OR 1.56; CI 1.11–2.18; P =.01), and distal duct margins (OR 43.25; CI 10.38–180.16; P <.01). SBDR yielded fewer lymph nodes (MD -6.93 nodes; CI -9.72–4.15; P <.01) and detected fewer nodal metastases (OR 0.72; CI 0.55–0.94; P =.01). SBDR portended less perioperative morbidity (OR 0.31; CI 0.21–0.46; P <.01), but not mortality (OR 0.52; CI 0.20–1.32; P =.17). SBDR was associated with locoregional recurrences (OR 1.88; CI 1.01–3.53; P =.02), and lymph node recurrences (OR 2.13; CI 1.42–3.2; P =.04). SBDR yielded decreased 5-year OS (OR 0.75; CI 0.65–0.85; P <.01). Despite decreased perioperative morbidity, SBDR appears to provide inferior oncologic control for BDC. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Enhanced Recovery ERP protocols (ERP) have improved surgical outcomes in patients undergoing elective colon cancer (CC) surgery; however, efficacy in different populations may vary. We examined the impact of an ERP in a population with high rates of obesity and multiple comorbidities. Methods: We performed a retrospective analysis of factors associated with postoperative complications (PoC) and length of stay (LOS) following CC surgery from 2011 to 2019 in a 5-hospital healthcare system which serves a population with higher rates of obesity (body mass index ≥30kg/m2) and multi-comorbidities, as compared to published studies. Univariable and multivariable analyses were performed. Results: A total of 408 elective CC surgery patients with complete oncologic surgical data were identified. Of these, 191 (46.81%) were under ERP. Factors independently associated with PoC included obesity (OR=1.66, P=.029), laparoscopic (OR=.52, P=.020), and hybrid (OR=.38, P=.012) versus open surgery and ASA (American Society of Anesthesiologists) class ≥3 (OR=1.98, P=.006). ERP did not impact PoC but was associated with a reduction in LOS (β=−1.02 days, 95%CI: −1.75 – -.30, P=.006). ERP had an impact on LOS in both the non-obese and obese groups (P<.001 and P=.034, respectively). PoC significantly increased LOS (β=6.67 days, 95%CI: 5.41-7.03, P<.001). Conclusions: Following elective CC surgery, obesity and medical comorbidities were associated with increased PoC and in turn, as expected, increased LOS. ERP was associated with a reduction in LOS in both obese and non-obese patients. In high-risk populations, application of ERP may be particularly important to optimize surgical outcomes following CC surgery. [ABSTRACT FROM AUTHOR]

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is used to treat colorectal cancer and can acutely induce metabolic dysfunction. However, the lasting effects on systemic and skeletal muscle metabolism after treatment cessation are poorly understood. Therefore, we investigated the acute and lasting effects of FOLFOX chemotherapy on systemic and skeletal muscle metabolism in mice. Direct effects of FOLFOX in cultured myotubes were also investigated. Male C57BL/6J mice completed four cycles (acute) of FOLFOX or PBS. Subsets were allowed to recover for 4 wk or 10 wk. Comprehensive Laboratory Animal Monitoring System (CLAMS) metabolic measurements were performed for 5 days before study endpoint. C2C12 myotubes were treated with FOLFOX for 24 hr. Acute FOLFOX attenuated body mass and body fat accretion independent of food intake or cage activity. Acute FOLFOX decreased blood glucose, oxygen consumption (VO2), carbon dioxide production (VCO2), energy expenditure, and carbohydrate (CHO) oxidation. Deficits in VO2 and energy expenditure remained at 10 wk. CHO oxidation remained disrupted at 4 wk but returned to control levels after 10 wk. Acute FOLFOX reduced muscle COXIV enzyme activity, AMPK(T172), ULK1(S555), and LC3BII protein expression. Muscle LC3BII/I ratio was associated with altered CHO oxidation (r = 0.75, P = 0.03). In vitro, FOLFOX suppressed myotube AMPK(T172), ULK1(S555), and autophagy flux. Recovery for 4 wk normalized skeletal muscle AMPK and ULK1 phosphorylation. Our results provide evidence that FOLFOX disrupts systemic metabolism, which is not readily recoverable after treatment cessation. FOLFOX effects on skeletal muscle metabolic signaling did recover. Further investigations are warranted to prevent and treat FOLFOX-induced metabolic toxicities that negatively impact survival and life quality of patients with cancer. [ABSTRACT FROM AUTHOR]

Background Minimally-invasive hepatectomy (MIH) is increasingly utilized; however, predictors and outcomes for patients requiring conversion to an open procedure have not been adequately studied. Methods The 2014–15 ACS-NSQIP database was analyzed. Unplanned conversion was compared to successful MIH and elective open hepatectomy. Results Among 6918 hepatectomies, 1062 (15.4%) underwent attempted MIH: 989 laparoscopic, 73 robotic. Conversion occurred in 203 (19.1%). Compared to successful MIH, patients requiring unplanned conversion experienced higher rates of complications (34.5% vs 14.6%, p < 0.001), including bile leaks (7.4% vs 2.8%, p = 0.002), organ space infection (6.4% vs 2.9%, p = 0.016), UTI (4.9% vs 1.2%, p = 0.002), perioperative bleeding (21.2% vs 6.1%, p < 0.001), DVT (3.0% vs 0.8%, p = 0.024), and sepsis (5.9% vs 1.9%, p = 0.001). Conversion led to greater LOS (5 days vs 3 days, p < 0.001) and 30-day mortality (3.0% vs 0.5%, p = 0.005). Compared to elective open hepatectomy, conversion was associated with greater perioperative bleeding (21.2% vs 15.3%, p = 0.037). On multivariate analysis, major hepatectomy (OR 2.21, p < 0.001), concurrent ablation (OR 1.79, p = 0.020), and laparoscopic approach (vs. robotic) (OR 3.22, p = 0.014) were associated with conversion. Conclusion Analysis of this national database revealed unplanned conversion during MIH is associated with greater morbidity and mortality. MIH should be approached cautiously in patients requiring major hepatectomy. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy (CTX) is associated with improved survival for patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). The current study evaluated the influence of tumor location on receipt of CTX.Methods: The NCDB (2006-2017) was queried to identify patients with clinical stage I-III PDAC. Predictors of receipt of CTX, sequencing of CTX, and overall survival (OS) were analyzed.Results: Among 14,557 patients who underwent resection for PDAC 3,453 (24%) did not receive CTX. On multivariable analysis, patients with tail tumors were 15% less likely to receive CTX (OR 0.85, 95% CI 0.747-0.968) and 58% less likely to receive neoadjuvant CTX (OR 0.42, 95% CI 0.351-0.509) relative to patients with head/neck tumors. For patients with body tumors, there was no difference in rates of administration or sequence of CTX. For patients with resected tail tumors, median OS was 29.9 vs 18.9 months (p < 0.001) between those who did and did not receive CTX. For patients with tail tumors, independent predictors of not receiving CTX, regardless of sequence, were increasing age (OR 0.95, 95% CI 0.935-0.965), increasing post-op length of stay (OR 0.95, 95% CI 0.932-0.968), and 30-day post-op readmission (OR 0.46, 95% CI 0.315-0.670).Conclusions: In patients with clinical stage I-III PDAC, tumor location within the tail was independently associated with not receiving CTX. Given the marked improvement in OS when CTX is administered, strategies aimed at increasing the number of these patients who receive CTX are necessary. [ABSTRACT FROM AUTHOR]

Background: National studies have reported racial and socioeconomic disparities in gastric cancer (GC) care. The current study evaluated adequate lymph node (LN) assessment (≥16 LNs) during resection for GC within a healthcare system servicing a socioeconomically disparate, mostly non-White population in the Southeast United States.Methods: A retrospective cohort study of patients undergoing resection for GC between 2003-2019 was performed. Factors associated with adequate LN assessment including patient and tumor characteristics were analyzed.Results: Among 202 patients, adequate LN assessment was performed in 97 (48%) patients. On univariable analysis, younger age, non-White race, lower Charlson Comorbidity Index (CCI), Medicaid or no insurance, D1+/D2 lymphadenectomy, clinical evidence of regional LN metastases, total gastrectomy, and receipt of neoadjuvant therapy were associated with adequate LN assessment. On multivariable analysis, non-White race (OR 2.79, 95% CI 1.38-5.65), CCI <4 (OR 2.14, 95% CI 1.15-3.96), and D1+/D2 lymphadenectomy (OR 3.63, 95% CI 1.96-6.74) were the only factors independently associated with adequate LN evaluation.Conclusions: In the current study, non-White race, independent of socioeconomics, was significantly associated with adequate LN assessment. Future work is necessary to improve standardization and achieve higher rates of adequate LN assessment for all patients during resection for GC. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant operative time, hospital resources, and morbidity. We examine factors associated with hospital length of stay (LOS) and early overall survival (OS) after CRS/HIPEC.Materials and Methods: Patients who underwent CRS/HIPEC were evaluated for factors associated with LOS. Institutional learning curve influence was addressed by comparing early vs late cohorts. Variables with P < .200 after univariate analysis were considered for inclusion in multivariate linear regression modeling. Independent factors associated with OS were evaluated using the Kaplan-Meier method.Results: Seventy patients underwent CRS/HIPEC (mean age 52.3 years, 64.3% female, and 68.6% Caucasian). Presence of any surgical complication was found in 26 (37.1%), 28 (40%) remained intubated postoperatively, and the mean Peritoneal Carcinomatosis Index (PCI) score was 14.4 (±10.4). Mean intensive care unit and hospital LOS were 2.9 days (±2.3) and 9.6 days (±3.6), respectively. After adjusting for covariates, only shorter time to postoperative ambulation (regression coefficient .92, P = .001) and early extubation (regression coefficient -1.90, P = .018) were associated with decreased hospital LOS on multivariate analysis. Immediate postoperative extubation conferred an independent early survival benefit on Kaplan-Meier analysis (mean OS 714.8 vs 473.4 days, P = .010). There was no difference in hospital LOS or OS between early and late cohorts.Conclusion: Early postoperative extubation and shorter time to ambulation are associated with decreased hospital LOS. Moreover, CRS/HIPEC patients extubated immediately postoperatively have an early survival benefit. Every effort should be made to achieve early postoperative extubation and mobilization in CRS/HIPEC patients. [ABSTRACT FROM AUTHOR]

Purpose: Immunotherapy, such as checkpoint inhibitors against anti-programmed death-ligand 1 (PD-L1), has not been successful in treating patients with pancreatic ductal adenocarcinoma (PDAC). Tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and the TGF-β cytokine are critical in anti-cancer immunity. We hypothesized that TGF-β enhances the immunosuppressive effects of TAM, MDSC, and DC presence in tumors. Methods: Using a murine PDAC cell line derived from a genetically engineered mouse model, we orthotopically implanted treated cells plus drug embedded in Matrigel into immunocompetent mice. Treatments included saline control, TGF-β1, or a TGF-β receptor 1 small molecule inhibitor, galunisertib. We investigated TAM, MDSC, DC, and TAM PD-L1 expression with flow cytometry in tumors. Separately, we used the TIMER2.0 database to analyze TAM and PD-L1 gene expression in human PDAC tumors in TCGA database. Results: TGF-β did not alter MDSC or DC frequencies in the primary tumors. However, in PDAC metastases to the liver, TGF-β decreased the proportion of MDSCs (P=0.022) and DCs (P=0.005). TGF-β significantly increased the percent of high PD-L1 expressing TAMs (32 ± 6 % vs. 12 ± 5%, P=0.013) but not the proportion of TAMs in primary and metastatic tumors. TAM PD-L1 gene expression in TCGA PDAC database was significantly correlated with tgb1 and tgfbr1 gene expression (P<0.01). Conclusions: TGF-β is important in PDAC anti-tumor immunity, demonstrating context-dependent impact on immune cells. TGF-β has an overall immunosuppressive effect mediated by TAM PD-L1 expression and decreased presence of DCs. Future investigations will focus on enhancing anti-cancer immune effects of TGF-β receptor inhibition. [ABSTRACT FROM AUTHOR]

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974-2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM. [ABSTRACT FROM AUTHOR]

Purpose: The transforming growth factor-beta (TGF-β) pathway plays a paradoxical, context-dependent role in pancreatic ductal adenocarcinoma (PDAC): a tumor-suppressive role in non-metastatic PDAC and a tumor-promotive role in metastatic PDAC. We hypothesize that non-SMAD-TGF-β signaling induces PDAC progression. Methods: We investigated the expression of non-SMAD-TGF-β signaling proteins (pMAPK14, PD-L1, pAkt and c-Myc) in patient-derived tissues, cell lines and an immunocompetent mouse model. Experimental models were complemented by comparing the signaling proteins in PDAC specimens from patients with various survival intervals. We manipulated models with TGF-β, gemcitabine (DNA synthesis inhibitor), galunisertib (TGF-β receptor inhibitor) and MK-2206 (Akt inhibitor) to investigate their effects on NF-κB, β-catenin, c-Myc and PD-L1 expression. PD-L1 expression was also investigated in cancer cells and tumor associated macrophages (TAMs) in a mouse model. Results: We found that tumors from patients with aggressive PDAC had higher levels of the non-SMAD-TGF-β signaling proteins pMAPK14, PD-L1, pAkt and c-Myc. In PDAC cells with high baseline β-catenin expression, TGF-β increased β-catenin expression while gemcitabine increased PD-L1 expression. Gemcitabine plus galunisertib decreased c-Myc and NF-κB expression, but induced PD-L1 expression in some cancer models. In mice, gemcitabine plus galunisertib treatment decreased metastases (p = 0.018), whereas galunisertib increased PD-L1 expression (p < 0.0001). In the mice, liver metastases contained more TAMs compared to the primary pancreatic tumors (p = 0.001), and TGF-β increased TAM PD-L1 expression (p < 0.05). Conclusions: In PDAC, the non-SMAD-TGF-β signaling pathway leads to more aggressive phenotypes, TAM-induced immunosuppression and PD-L1 expression. The divergent effects of TGF-β ligand versus receptor inhibition in tumor cells versus TAMs may explain the TGF-β paradox. Further evaluation of each mechanism is expected to lead to the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Centralized care for patients with pancreatic cancer is associated with longer survival. We hypothesized that increased travel distance from home is associated with increased survival for pancreatic cancer patients.Methods: The National Cancer Database user file for all pancreatic cancer patients was investigated from 2004 through 2015. Distance from the patients' zip code to the treating facility was determined. Survival was investigated using the Kaplan-Meier method. Cox hazard ratios (CoxHRs) were determined based on stage of disease, distance traveled for care, and clinical factors.Results: 340 780 patients were identified. In the average age of 68 ± 12 years, 51% were male and 83% were Caucasian. For all stages of cancer, longer survival was associated with traveling farther (P < .001). The survival advantage was longer for Caucasians than African Americans (3.7 months vs. 2.6 months, P < .001) Travel was associated with a 13% decrease in risk of death (P < .001). Even controlling for the pathologic stage, traveling farther was associated with decreased risk of death (CoxHR = .91, P < .001).Discussion: Traveling for care is associated with improved survival for pancreatic cancer patients. While a selection bias may exist, the fact that all stages of patients investigated benefited suggests that this is a real phenomenon. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD) is primarily a disease of massive lymphadenopathy and sinus histiocytosis. It has been documented across extranodal organ systems, but it rarely has been described in the gastrointestinal tract only. Here is the unique case of 2 primary extra-nodal masses found simultaneously in the pancreas and right colon of a patient without the classical concomitant lymphadenopathy. We also reviewed the literature and found 11 additional cases of pancreatic RDD. This is the first male case and 1 of only 2 cases of RDD presenting synchronously in 2 distinct locations within the gastrointestinal system. Furthermore, we discuss the potential use of fine needle aspiration (FNA) and core sample biopsies in confirming a diagnosis of RDD. [ABSTRACT FROM AUTHOR]

Background: In the United States, patients with clinical stage II or III rectal cancer typically receive neoadjuvant chemoradiation therapy (chemo/XRT) over a 5-6 week period followed by a 6-10 week break prior to proctectomy. In the current study, we evaluate the utilization of restaging studies performed and detection of disease progression during this window.Methods: A retrospective review of patients with clinical stage II/III rectal cancer was performed. Medical records were analyzed to collect clinicopathologic data and the performance and results of preoperative, early postoperative, and first surveillance CT and/or PET/CT in patients completing long course neoadjuvant chemo/XRT and undergoing proctectomy.Results: Between 2005 and 2017, 176 patients with clinical stage II or III rectal adenocarcinoma completed neoadjuvant chemo/XRT and underwent proctectomy. Preoperative restaging with CT CAP and/or CT/PET was performed in 72 (40.9%) patients with no detection of disease progression. Of the 104 patients without preoperative restaging, 1 had intraoperative detection of liver metastases and 31 had early postoperative reimaging (within 30 days of proctectomy) of which 2 had detection of new pulmonary metastases. Among 72 patients with no preoperative or early postoperative reimaging, first surveillance imaging was available in 47 and detected new metastases in 8 (17%).Discussion: In patients with clinical stage II/III rectal cancer who undergo long course neoadjuvant chemo/XRT, perioperative reimaging with CT CAP and/or PET/CT detects new metastases in a small percentage of patients. A multi-institutional, prospective analysis using standardized staging protocols is warranted to better determine the value of preoperative restaging in these patients. [ABSTRACT FROM AUTHOR]

Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined. The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated. Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005). This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection. [ABSTRACT FROM AUTHOR]

Background: In the USA, most patients with clinical stage II/III rectal cancer receive neoadjuvant chemoradiation (chemo/XRT) over 5–6 weeks followed by a 6–10-week break before proctectomy. As chemotherapy is delivered at radio-sensitizing doses, there is essentially a 3-month window during which potential systemic disease is untreated. Evidence regarding the utility of restaging patients prior to proctectomy is limited. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies evaluating the utility of restaging patients with rectal cancer after completion of long-course chemo/XRT, and reporting associated changes in management. Studies that were non-English, included <50 patients, or examining the diagnostic accuracy of imaging modalities were excluded. Study quality was evaluated using the modified Newcastle Ottawa Scale. Results: Eight studies were identified including a total of 1251 patients restaged between completion of chemo/XRT and proctectomy. All studies were retrospective. Restaging identified new metastatic disease in 72 (6.0%) patients, with 4 studies reporting specific sites: liver (n = 28), lung (n = 8), adrenal (n = 1), bone (n = 1), and multiple sites (n = 7). Overall progression (distant or local) was detected in 88 (7.0%) patients and resulted in a change in management in 77 (87.5%) of these patients. Tumor-related prognostic characteristics were inconsistently reported among studies, precluding meta-analysis. Conclusions: Although restaging between completion of neoadjuvant chemo/XRT and proctectomy detects disease progression in only a small percentage of patients, findings alter the treatment plan in the vast majority of these patients. Multi-institutional collaboration with analysis of well-defined prognostic variables may better identify patients most likely to benefit from restaging. [ABSTRACT FROM AUTHOR]

Clinically lymph node positive (cLNP) intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, without clear management guidelines for the practicing clinician. We sought to evaluate current practice patterns for cLNP ICC, including associations with survival. The National Cancer Database was queried for patients with cLNP ICC, without extrahepatic metastases. We identified 1023 patients with cLNP ICC, 77%% (n = 784) of whom received chemotherapy alone. Resection was undertaken in 23% (n = 239) of patients and was most commonly utilized in combination with chemotherapy (n = 150). Median survival for all patients was 13.6 months. Patients undergoing resection in combination with chemotherapy were associated with an improved survival (22.5 months) as compared to those patients receiving chemotherapy alone (11.9 months) or resection alone (12.4 months) (p < 0.01). Finally, we compared the survival of patients with cLNP ICC with that of patients with pathologically proved lymph node positive (pLNP) ICC, all of whom were treated with resection with chemotherapy, and found no difference in survival (22.5 months–19.3 months, p = 0.99, respectively). While the decision to pursue resection for ICC is multifactorial and patient specific, the presence of clinically positive LNs should not represent a contraindication. [ABSTRACT FROM AUTHOR]

Clinically relevant pancreatic fistula (CR-POPF), after distal pancreatectomy (DP), remains a clinical challenge. Prior studies investigating the relationship between BMI and CR-POPF have yielded conflicting results. We hypothesized that BMI is associated with CR-POPF in patients having DP for pancreatic ductal adenocarcinoma (PDAC). Patients who underwent DP for PDAC at a single institution from 2006 to 2018 were retrospectively reviewed. A CR-POPF was defined as International Study Group of Pancreatic Surgery (ISGPS) grade B or C fistula. Uni- and multivariable logistic regression analysis assessed factors associated with CR-POPF after DP. Seventy-eight patients met the inclusion criteria, 51 per cent were female, 51 per cent were white, and the average age was 59 ± 15 years. The median BMI was 26 (IQR 24-29). Of all, 19 per cent (n = 15) of patients had a CR-POPF. With a mean follow-up of 2.8 ± 2.5 years, the presence of a CR-POPF was not associated with survival (P = 0.17). On univariable logistic regression, older age was associated with a decreased risk of CR-POPF (odds ratio (OR) = 0.95, P = 0.015). Increasing BMI was associated with an increased risk of CR-POPF (OR = 1.1, P = 0.044). On multivariate analysis, after controlling for multiple factors, BMI (OR = 1.12, P = 0.035) was the only factor associated with the development of a CR-POPF, whereas older age (OR = 0.94, P < 0.001) was slightly protective. Increasing BMI is associated with an increased risk of CR-POPF after DP for PDAC. These findings should be considered during preoperative counseling. Efforts to diminish the risk of CR-POPF should be focused on patients with higher BMI. [ABSTRACT FROM AUTHOR]

Abstract Background Minimally invasive pancreatic resection (MIPR) is being increasingly utilized. Outcomes for patients experiencing unplanned conversion to an open procedure during MIPR have been incompletely assessed. We sought to determine the short-term outcomes and factors associated with unplanned conversion during MIPR. Methods A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy-targeted data set was conducted. Successful MIPR was compared with unplanned conversion. Propensity matching was used to separately compare unplanned conversion during MIPR with planned open pancreatectomy. Results Unplanned conversion occurred in 24.6% of 350 attempted minimally invasive pancreatoduodenectomy (MIPD) and 19.6% of 1174 attempted minimally invasive distal pancreatectomy (MIDP). Conversion was associated with greater overall morbidity and 30-day mortality compared with successful MIPR for both MIPD and MIDP. After matching, unplanned conversion resulted in outcomes equivalent or inferior to open pancreatectomy. Factors significantly associated with unplanned conversion during MIPD included intermediate gland texture, vascular resection, hypertension, disseminated cancer, and chronic steroid use. For MIDP, male sex, hard gland texture, vascular resection, smoking, and recent weight loss were independently associated with conversion. A robotic approach was inversely associated with conversion for MIPD and MIDP. Conclusions Unplanned conversion during MIPR is associated with greater morbidity and 30-day mortality. Conversion resulted in outcomes that, at best, mimicked those of open pancreatectomy. Several risk factors including the need for vascular resection are associated with unplanned conversion and should be acknowledged when planning an operative approach. [ABSTRACT FROM AUTHOR]

Background Potentially curative treatment for gastrointestinal stromal tumors (GIST) involves resection with selective utilization of tyrosine kinase inhibitors. A potential association between obesity and GIST has been postulated as GIST is among the most common incidental findings during gastric resection for bariatric procedures. The purpose of this study is to investigate the relationship and impact of obesity on the pathologic and short-term outcomes in patients with GIST. Methods We performed a retrospective review of patients with resected GIST. The impact of obesity, defined as body mass index (BMI) ≥30 kg/m 2 , on pathologic results and short-term outcomes was evaluated. Results Sixty-one patients underwent resection with a median follow-up of 26 mo (1-129 mo). Disease involved the stomach (74%), small intestine (18%), or colon/rectum (5%). Median tumor size was 6 cm, and 13 patients (21%) underwent multivisceral resection. Median BMI for the cohort was 27.2 kg/m 2 , and 24 patients (39%) were classified as obese based on BMI. Nonobese patients were noted to have larger primary tumors (median: 7 cm versus 5 cm, P = 0.02) and undergo multivisceral resection more frequently (32.4% versus 4.2%, P < 0.01). Short-term outcomes were similar between the groups, with a slight trend toward more postoperative complications among the obese patients. Conclusions In this study, obese patients tended to have more favorable pathologic features. GISTs may represent another example of the “obesity paradox” in which obesity seemingly provides a protective effect. Larger studies are warranted to verify the impact of obesity on outcomes and to elucidate any underlying clinicopathologic/biologic factors. [ABSTRACT FROM AUTHOR]

Background: Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases. Study Design: A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. Results: There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003). Conclusions: Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined. [Copyright &y& Elsevier]

Highlights from the article: A computed tomography (CT) scan demonstrated a 4.7 cm × 4.2 cm mass (averaging - 95 Hounsfield units (HU), consistent with the density of fat tissue) in the head of the pancreas, suggestive of a lipoma (Fig. When evaluating a lipomatous lesion of the pancreas, it is important to distinguish between fatty infiltration (also known as lipomatosis), lipoma, and liposarcoma. 3 Raut CP, Fernandez-del Castillo C. Giant lipoma of the pancreas: case report and review of lipomatous lesions of the pancreas.