A Modified Floxuridine Reduced-Dose Protocol for Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

BACKGROUND: Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection. PATIENTS AND METHODS: We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts. RESULTS: Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP. CONCLUSIONS: A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance.

Liver-First Resection in Patients With Synchronous Colorectal Liver Metastases Is Associated with Inferior Recurrence-Free Survival: Reconsidering the Importance of the Primary Cancer.

BACKGROUND: Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based upon treatment sequencing are understudied. OBJECTIVE: This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the three treatment strategies, with respect to early or delayed removal of the primary tumor. DESIGN: Retrospective analysis of prospectively maintained database, with 1:1 propensity-matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches. SETTINGS: Single-institution, tertiary cancer center. PATIENTS: Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003-2019. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. Median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by three-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not significantly differ between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28/simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3-year: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3-years (79% versus 80%, p = 0.95) or 5-years (59% versus 59%, p > 0.99). LIMITATIONS: This study has a retrospective design and limited sample size. CONCLUSIONS: A liver-first approach is associated with worse recurrence free-survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. Prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection is recommended. See Video Abstract.

Combinatorial Inhibition of Complement Factor D and BCL2 for Early-Onset Colorectal Cancer.

BACKGROUND: The tumor immune microenvironment is distinct between early-onset and late-onset colorectal cancer, which facilitates tumor progression. We previously identified several genes, including complement factor D, as having increased expression in patients with early-onset colorectal cancer. OBJECTIVE: This study aimed to assess and validate the differential expression of immune genes in early-onset and late-onset colorectal cancer. We also aimed to test known drugs targeting genes increased in early-onset colorectal cancer in preclinical mouse models. DESIGN: A retrospective cohort study with analysis was performed using tumor RNA from formalin-fixed paraffin-embedded cell culture and immunohistochemistry to validate gene expression and function and in vivo preclinical tumor study to assess drug efficacy. SETTINGS: The Oregon Colorectal Cancer Registry was queried to identify patients with colorectal cancer. PATIENTS: The study included 67 patients with early-onset colorectal cancer and 54 patients with late-onset colorectal cancer. INTERVENTIONS: Preclinical animal models using the HCT-116 colon cancer cell line were treated with the complement factor D inhibitor danicopan and the BCL2 inhibitor venetoclax, or with vehicle controls. MAIN OUTCOME MEASURES: Elevated RNA signatures using NanoString data were evaluated by the retrospective cohort. When inhibiting these markers in the mouse preclinical model, tumor volume and weight were the main outcome measures. RESULTS: After updating our sample size from our previously published data, we found that complement factor D and BCL2, genes with known function and small molecule inhibitors, are elevated in patients with early-onset colorectal cancer. When inhibiting these markers with the drugs danicopan and venetoclax in a mouse model, we found that the combination of these drugs decreased tumor burden but also resulted in toxicity. LIMITATIONS: This study is limited by a small sample size and a subcutaneous tumor model. CONCLUSIONS: Combinatorial inhibition of early-onset associated genes complement factor D and BCL2 slows the growth of early-onset colorectal cancer in a mouse preclinical model. See Video Abstract . INHIBICIN COMBINADA DEL FACTOR DCOMPLEMENTARIO Y DEL BCL EN CASOS DE CNCER COLORRECTAL DE APARICIN TEMPRANA: ANTECEDENTES:El microambiente inmunológico del tumor es distinto entre el cáncer colorrectal de aparición temprana y el de aparición tardía, lo que facilita la progresión de dicho tumor. Anteriormente identificamos varios genes, incluidos el factor D-Complementario, con una mayor expresión en pacientes con cáncer colorrectal de aparición temprana.OBJETIVO:El presente estudio tuvo como objetivo el evaluar y validar la expresión diferenciada de genes inmunes en casos de cáncer colorrectal de aparición temprana y tardía. También nos propusimos evaluar los fármacos conocidos dirigidos sobre los genes aumentados en el cáncer colorrectal de aparición temprana en modelos pre-clínicos en ratones.DISEÑO:Estudio de cohortes con análisis retrospectivo utilizando el ARN tumoral procedente de cultivos celulares fijados con formalina e incluidos en parafina, y el analisis por inmunohistoquímica para validar la expresión y la función genética. Se realizó el estudio pre-clínico de los tumores in vivo para evaluar la eficacia de los fármacos.AJUSTES:Se consultó el Registro de Oregon de casos de Cáncer Colorrectal para encontrar los pacientes afectados.SUJETOS:67 pacientes con cáncer colorrectal de aparición temprana y 54 pacientes con cáncer colorrectal de aparición tardía.INTERVENCIONES (SI LAS HUBIESE):Los modelos animales pre-clínicos que utilizaron la línea celular de cáncer de colon HCT-116 se trataron con el inhibidor del factor D-Complementario o Danicopan y con el inhibidor de BCL-2 o Venetoclax, ambos con control del transportador.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las firmas de ARN elevadas utilizando los datos del NanoString a partir de la cohorte retrospectiva. Al inhibir estos marcadores del modelo pre-clínico en los ratones, el volumen y el peso del tumor fueron las principales medidas de resultado.RESULTADOS:Después de actualizar el tamaño de nuestra muestra a partir de datos publicados con anterioridad, encontramos que el factor D-Complementario y BCL-2, genes con función conocida e inhibidores de moléculas pequeñas, se encuentran elevados en aquellos pacientes con cáncer colorrectal de aparición temprana. Al inhibir estos marcadores con los medicamentos Danicopan y Venetoclax en el modelo de ratones vivos, encontramos que la combinación de estos dos farmacos disminuyó la carga tumoral pero también produjo toxicidad.LIMITACIONES:Estudio limitado por un tamaño de muestra pequeño y el modelo de tumor subcutáneo.CONCLUSIONES:La inhibición combinada de genes asociados de aparición temprana, el factor D-Complementario y el BCL-2, enlentecen el crecimiento del cáncer colorrectal de aparición temprana del modelo preclínico en ratones. (Traducción-Dr. Xavier Delgadillo ).

Exploratory Analyses of Circulating Neoplastic-Immune Hybrid Cells as Prognostic Biomarkers in Advanced Intrahepatic Cholangiocarcinoma.

Existing clinical biomarkers do not reliably predict treatment response or disease progression in patients with advanced intrahepatic cholangiocarcinoma (ICC). Circulating neoplastic-immune hybrid cells (CHCs) have great promise as a blood-based biomarker for patients with advanced ICC. Peripheral blood specimens were longitudinally collected from patients with advanced ICC enrolled in the HELIX-1 phase II clinical trial (NCT04251715). CHCs were identified by co-expression of pan-cytokeratin (CK) and CD45, and levels were correlated to patient clinical disease course. Unsupervised machine learning was then performed to extract their morphological features to compare them across disease courses. Five patients were included in this study, with a median of nine specimens collected per patient. A median of 13.5 CHCs per 50,000 peripheral blood mononuclear cells were identified at baseline, and levels decreased to zero following the initiation of treatment in all patients. Counts remained undetectable in three patients who demonstrated end-of-trial clinical treatment response and conversely increased in two patients with evidence of therapeutic resistance. In the post-trial surveillance period, interval counts increased prior to or at the time of clinical progression in three patients and remain undetectable in one patient with continued long-term disease stability. Using our machine learning platform, treatment-resistant CHCs exhibited upregulation of CK and downregulation of CD45 relative to treatment-responsive CHCs. CHCs represent a promising blood-based biomarker to supplement traditional radiographic and biochemical measures.

Rapid metastatic recurrence after pancreatic cancer resection: a multi-center, regional analysis of trends in surgical failure over two decades.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAc) is a lethal malignancy, attributed in part to high rates of rapid recurrence (rrPDAc) following resection. We sought to characterize recurrence rates over time and investigate factors predictive of rrPDAc. METHODS: A regional multi-institutional cancer registry, augmented with data from the National Surgical Quality Improvement Program database, was queried for patients with PDAc from 1996 to 2020. rrPDAc was defined as recurrence within 6 months following curative-intent resection. RESULTS: We identified 924 patients who underwent resection for PDAc; rrPDAc occurred in 236 (26%) patients. Median incidence of rrPDAc was 25.3% (IQR 22-30.2%) per year. Median survival in rrPDAc, non-rapid recurrence, and no recurrence was 10.3, 25.2, and 56.1 months respectively (p < 0.001). Variables independently associated with greater odds of rrPDAc included surgical site infection (SSI) (OR 2.06) and nodal positivity (OR 2.05); adjuvant therapy was associated with lower odds (OR 0.38). Neoadjuvant chemotherapy did not alter risk of rrPDAc. Three-year post-recurrence survival was no different in rrPDAc versus those without. CONCLUSION: Despite therapeutic advances, incidence of rrPDAc remains unchanged. SSIs and nodal positivity are independently associated with increased risk of rrPDAc, while adjuvant chemotherapy is associated with lower risk. Strategies focused on preventing rapid recurrence may improve survival.

Care at high-volume centers is associated with improved outcomes for patients with pancreatic neuroendocrine tumors: A population-level analysis.

BACKGROUND AND OBJECTIVES: Primary resection and debulking of liver metastases have been associated with improved survival in pancreatic neuroendocrine tumors (PNETs). The treatment patterns and outcomes differences between low-volume (LV) institutions and high-volume (HV) institutions remains unstudied. METHODS: A statewide cancer registry was queried for patients with nonfunctional PNET from 1997 to 2018. LV institutions were defined as treating <5 newly diagnosed patients with PNET per year, while HV institutions treated ≥5. RESULTS: We identified 647 patients: 393 with locoregional (n = 236 HV care, n = 157 LV care) and 254 with metastatic disease (n = 116 HV care, n = 138 LV care). Patients with HV care had improved disease-specific survival (DSS) compared to patients with LV care for both locoregional (median 63 vs. 32 months, p < 0.001) and metastatic disease (median 25 vs. 12 months, p < 0.001). In patients with metastatic disease, primary resection (hazard ratio [HR]: 0.55, p = 0.003) and HV institution (HR: 0.63, p = 0.002) were independently associated with improved DSS. Furthermore, diagnosis at a HV center was independently associated with higher odds of receiving primary site surgery (odds ratio [OR]: 2.59, p = 0.01) and metastasectomy (OR: 2.51, p = 0.03). CONCLUSIONS: Care at HV centers is associated with improved DSS in PNET. We recommend referral of all patients with PNETs to HV centers.

Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. METHODS: A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. RESULTS: Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC-alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5-fluorouracil versus gemcitabine-based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism-specific changes or antibiotic resistance patterns. CONCLUSIONS: Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.

Medical Management of Inflammatory Bowel Disease.

The past few decades have seen significant advancements in the medical management of both ulcerative colitis (UC) and Crohn's disease (CD). The previous dependence on steroids is no longer an acceptable strategy following the Food and Drug Administration approval for several new classes of medication. These medications include aminosalicylates, immunomodulators, biologics, and oral targeted small-molecule inhibitors. This article highlights several key trials and discusses modern treatment paradigms for both UC and CD based on disease severity.

Minimally invasive umbilical hernia repair is safe for patients with liver dysfunction: A propensity-score-matched analysis of approach and outcomes using ACS-NSQIP.

BACKGROUND: Umbilical hernias are highly prevalent in patients with liver dysfunction, ascites, and cirrhosis. This patient population carries significant perioperative risk and poses significant challenges because of their comorbidities. Literature suggests that elective repair of umbilical hernias can lead to better outcomes by reducing the risk of ascitic leak and compromised bowel. Medical optimization followed by open repair has been the standard approach; however, little is known about whether a laparoscopic approach may be equivalent or superior. METHODS: We retrospectively analyzed the American College of Surgeons National Surgical Quality Improvement Program database from 2015 to 2021 for umbilical hernia repairs in patients with liver dysfunction, as defined per the aspartate aminotransferase to platelet ratio index ≥1. We compare operative outcomes for open and laparoscopic repair, adjusting for confounders using propensity score matching and stratifying by case acuity. RESULTS: We identified 1,983 patients with liver dysfunction who underwent umbilical hernia repair. Most patients (86%) were operated via an open approach rather than laparoscopy. Operative outcomes between the laparoscopy and open group were comparable regarding mortality and serious complications. Notably, length of stay and need for blood transfusion intraoperatively or postoperatively were reduced in the laparoscopy group (P < .001). These findings remained significant after subgroup analysis with propensity matching stratified by elective and emergency case types. CONCLUSION: Minimally invasive umbilical hernia repair in liver dysfunction is as safe and, in some metrics, superior to open technique. We found no difference in mortality although hospital stays and the need for blood transfusions were lower in the laparoscopy groups. Prospective randomized trials are needed to validate these findings further.

Colorectal Disease and the Gut Microbiome: What a Surgeon Needs to Know.

The gut microbiome is defined as the microorganisms that reside within the gastrointestinal tract and produce a variety of metabolites that impact human health. These microbes play an intricate role in human health, and an imbalance in the gut microbiome, termed gut dysbiosis, has been implicated in the development of varying diseases. The purpose of this review is to highlight what is known about the microbiome and its impact on colorectal cancer, inflammatory bowel disease, constipation, Clostridioides difficile infection, the impact of bowel prep, and anastomotic leaks.

Referral and treatment patterns in pancreatic acinar cell carcinoma: A regional population-level analysis.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. METHODS: We queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. RESULTS: 43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p â€‹= â€‹0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p â€‹< â€‹0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n â€‹= â€‹4) and limited to advanced (stage III/IV) disease. CONCLUSION: Stage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

Clinician overconfidence in visual estimation of the posthepatectomy liver remnant volume: A proximal source of liver failure after major hepatic resection?

BACKGROUND: Post-hepatectomy liver failure is a source of morbidity and mortality after major hepatectomy and is related to the volume of the future liver remnant. The accuracy of a clinician's ability to visually estimate the future liver remnant without formal computed tomography liver volumetry is unknown. METHODS: Twenty physicians in diagnostic radiology, interventional radiology, and hepatopancreatobiliary surgery reviewed 20 computed tomography scans of patients without underlying liver pathology who were not scheduled for liver resection. We evaluated clinician accuracy to estimate the future liver remnant for 3 hypothetical major hepatic resections: left hepatectomy, right hepatectomy, and right trisectionectomy. The percent-difference between the mean and actual computed tomography liver volumetry (mean percent difference) was tested along with specialty differences using mixed-effects regression analysis. RESULTS: The actual future liver remnant (computed tomography liver volumetry) remaining after a hypothetical left hepatectomy ranged from 59% to 75% (physician estimated range: 50%-85%), 23% to 40% right hepatectomy (15%-50%), and 13% to 29% right trisectionectomy (8%-39%). For right hepatectomy, the mean future liver remnant was overestimated by 95% of clinicians with a mean percent difference of 22% (6%-45%; P < .001). For right trisectionectomy, 90% overestimated the future liver remnant by a mean percent difference of 25% (6%-50%; P < .001). Hepatopancreatobiliary surgeons overestimated the future liver remnant for proposed right hepatectomy and right trisectionectomy by a mean percent difference of 25% and 34%, respectively. Based on years of experience, providers with <10 years of experience had a greater mean percent difference than providers with 10+ years of experience for hypothetical major hepatic resections, but was only significantly higher for left hepatectomy (9% vs 6%, P = .002). CONCLUSION: A clinician's ability to visually estimate the future liver remnant volume is inaccurate when compared to computed tomography liver volumetry. Clinicians tend to overestimate the future liver remnant volume, especially in patients with a small future liver remnant where the risk of posthepatectomy liver failure is greatest.

Calcium phosphate deposition, tertiary hyperparathyroidism, and the long-term effect on kidney allografts.

BACKGROUND: Tertiary hyperparathyroidism adversely affects kidney allografts, with calcium phosphate deposition hypothesized to be an underlying cause. We analyzed allograft biopsies to investigate risk factors for calcium phosphate deposition and understand its impact on allograft function. METHODS: We reviewed patients who underwent kidney transplantation from 2017 to 2019. Tertiary hyperparathyroidism was defined as an elevated parathyroid hormone and hypercalcemia beyond 3 months' posttransplant or being prescribed cinacalcet. Allograft failure was defined as needing dialysis posttransplantation or retransplantation beyond 3 months' posttransplant. Three- and 12-month allograft biopsies were reviewed for calcium phosphate deposition. The χ2, t-test, and multivariate regression were used for statistical analysis. RESULTS: Of 159 patients who underwent kidney transplantation, 59 (37.1%) were diagnosed with tertiary hyperparathyroidism. Longer preoperative dialysis vintage (odds ratio, 1.47; confidence interval, 1.22-1.80 P < .001) and preoperative cinacalcet usage (odds ratio, 18.4; confidence interval, 7.24-53.0 P < .001) were associated with tertiary hyperparathyroidism. In total, 36 of 59 (61%) patients with tertiary hyperparathyroidism had calcium phosphate deposition on 3- or 12-month kidney allograft biopsy compared with 23 of 100 (23%) patients without tertiary hyperparathyroidism (P < .001). Tertiary hyperparathyroidism (odds ratio, 6.01; confidence interval, 2.91-13.0 P < .001) was associated with calcium phosphate deposition. Calcium phosphate deposition and tertiary hyperparathyroidism were not associated with worse glomerular filtration rate at 3 years' posttransplantation. Of those with data available at 3 years' posttransplantation, 21 of 49 (42.9%) patients remained on cinacalcet. There were 3 of 159 (2%) patients who had allograft failure, 2 of whom had both tertiary hyperparathyroidism and calcium phosphate deposition. CONCLUSION: Preoperative variables associated with tertiary hyperparathyroidism included longer dialysis vintage and cinacalcet use. Tertiary hyperparathyroidism was the main risk factor for calcium phosphate deposition posttransplantation. In our population, calcium phosphate deposition and tertiary hyperparathyroidism were not significantly associated with lower glomerular filtration rate.

Role of genomics in intrahepatic cholangiocarcinoma for liver-directed therapy.

Only a minority of patients with intrahepatic cholangiocarcinoma are candidates for curative resection. Even those with disease limited to the liver may not be surgical candidates due to patient, liver, and tumor factors, including comorbidities, intrinsic liver disease, inability to establish a future liver remnant, and tumor multifocality. In addition, even after surgery, recurrence rates are high, with the liver being a predominant site of relapse. Lastly, tumor progression in the liver can sometimes result in demise for those with advanced disease. Therefore, it is not surprising that non-surgical, liver-directed therapies have emerged as both primary and complementary treatments for intrahepatic cholangiocarcinoma for multiple stages. Liver-directed therapies can be performed directly into the tumor via thermal or non-thermal ablation, catheter-based infusion into the hepatic artery containing either cytotoxic chemotherapy or radioisotope bearing spheres/beads, or delivered via external beam radiation. Presently, these therapies' selection criteria have been based on tumor size, location, liver function, and referral to particular specialists. In recent years, molecular profiling of intrahepatic cholangiocarcinoma has revealed a high rate of actionable mutations, and several targeted therapies have been approved for treatment in the second-line metastatic setting. However, little is known about these alterations' role in localized disease treatments. Therefore, we will review the current molecular landscape of intrahepatic cholangiocarcinoma and how it has been applied to liver-directed therapy.

High-volume centers are associated with higher receipt of combined therapy in stage III pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at a locally advanced stage with vascular involvement which was previously viewed as a contraindication to resection. However, high-volume centers are increasingly capable of resecting complex tumors. We aimed to explore patterns of treatment that are uncharacterized on a population level. METHODS: A statewide registry was queried from 2003 to 2018 for stage III PDAC. Stepwise logistic regression and Kaplan-Meier were used for statistical analysis. RESULTS: We identified 424 eligible patients. 348 (82%) received chemotherapy, 17 (4.0%) received resection, and 59 (13.9%) received both; median survival was 10.7, 8.7, and 22.7 months, respectively (P < 0.001). High-volume centers (≥20 cases per year; OR 5.40 [95% CI: 2.76, 10.58], P < 0.001) and later year of diagnosis (OR 1.12/year [95% CI: 1.04, 1.20], P = 0.004) were associated with higher odds of receiving combined therapy. CONCLUSION: PDAC patients with vascular involvement who receive both systemic chemotherapy and surgical resection have improved overall survival. High-volume centers are independently associated with higher odds of receiving combined systemic therapy and surgical resection.

Delayed adjuvant endocrine therapy is associated with decreased recurrence-free survival following neoadjuvant chemotherapy for breast cancer.

BACKGROUND: In hormone receptor-positive breast cancer (HRPBC), endocrine therapy is often initiated after adjuvant radiotherapy given concerns of radiation fibrosis. No studies have investigated how this may impact outcomes in high-risk patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Females with nonmetastatic HRPBC receiving NAC from 2011 to 2017 were identified from our multi-institutional database. Interval from surgery to endocrine therapy (ISET) was calculated in weeks. Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Of 280 patients, 179 (64%) received adjuvant radiotherapy; all deaths (n = 25) and 90% (n = 27) of recurrences occurred in this group, which was the focus of subsequent analysis. Median follow-up was 49 months. Recurrences were predominantly distant metastases (n = 21, 81%). Median ISET was 12 weeks (range 0-55 weeks). On multivariable analysis, ISET >14 weeks was independently associated with worse RFS (HR 3.20, 95% C.I. 1.22-8.40, P = 0.02) but not OS (HR 2.15, 95% C.I. 0.75-6.15, P = 0.15). CONCLUSION: In patients with HRPBC treated with NAC and adjuvant radiation, increasing ISET is associated with adverse oncologic outcomes.

Gut microbial metabolites and its impact on human health.

One of the primary methods by which the gut microbiome interacts with its host is through the interactions that occur through the production of the metabolites produced, either directly, or indirectly, through microbial metabolism. Decades of research has demonstrated that these metabolic products play a vital role in human health, either for its benefit or detriment. This review article highlights the main metabolites produced by the interactions between diet and the gut microbiome, bile acids and the gut microbiome, and products produced by the gut microbiome alone. Additionally, this article reviews the literature on the effects that these metabolites play on human health.